User login
Dapagliflozin may cut risk of HF hospitalization in patients with type 2 diabetes
Background: Dapagliflozin is a selective inhibitor of sodium-glucose transporter 2 (SGLT2) in the kidney; the drug blocks glucose reabsorption in the proximal tubule. It is taken once daily by mouth. An initial study sponsored by AstraZeneca was published January 2019 in the New England Journal of Medicine – “Dapagliflozin and cardiovascular outcomes in type 2 diabetes.” Until recently there was not an FDA-approved indication for the drug.
Study design: Randomized, double-blind, placebo-controlled trial.
Setting: 882 clinical sites in 33 countries.
Synopsis: The study randomized approximately 17,000 patients to receive either dapagliflozin or placebo in addition to any other diabetes treatments prescribed by their physician. This study demonstrated its primary safety outcome, which was that patients on dapagliflozin did not have any more major adverse cardiac events (MACE), compared with placebo. There were two primary efficacy outcomes. First, there was no change in MACE with dapagliflozin, compared with placebo. Second, and pertinent to this drug’s approval, was that dapagliflozin reduced risk of hospitalization for heart failure (HF) from 5.8% to 4.9%, compared to placebo; this includes both HF with both preserved and reduced ejection fractions.
Bottom line: Dapagliflozin now has an FDA-approved indication to reduce hospitalizations for HF in patients with type 2 diabetes. Based on this study, the number needed to treat with dapagliflozin is 111 patients to prevent one hospitalization for HF.
Citation: Farxiga approved in the US to reduce the risk of hospitalization for heart failure in patients with type-2 diabetes. AstraZeneca Press Release, 2019 Oct 21.
Dr. Como is a hospitalist and clinical instructor of medicine at the University of Utah, Salt Lake City.
Background: Dapagliflozin is a selective inhibitor of sodium-glucose transporter 2 (SGLT2) in the kidney; the drug blocks glucose reabsorption in the proximal tubule. It is taken once daily by mouth. An initial study sponsored by AstraZeneca was published January 2019 in the New England Journal of Medicine – “Dapagliflozin and cardiovascular outcomes in type 2 diabetes.” Until recently there was not an FDA-approved indication for the drug.
Study design: Randomized, double-blind, placebo-controlled trial.
Setting: 882 clinical sites in 33 countries.
Synopsis: The study randomized approximately 17,000 patients to receive either dapagliflozin or placebo in addition to any other diabetes treatments prescribed by their physician. This study demonstrated its primary safety outcome, which was that patients on dapagliflozin did not have any more major adverse cardiac events (MACE), compared with placebo. There were two primary efficacy outcomes. First, there was no change in MACE with dapagliflozin, compared with placebo. Second, and pertinent to this drug’s approval, was that dapagliflozin reduced risk of hospitalization for heart failure (HF) from 5.8% to 4.9%, compared to placebo; this includes both HF with both preserved and reduced ejection fractions.
Bottom line: Dapagliflozin now has an FDA-approved indication to reduce hospitalizations for HF in patients with type 2 diabetes. Based on this study, the number needed to treat with dapagliflozin is 111 patients to prevent one hospitalization for HF.
Citation: Farxiga approved in the US to reduce the risk of hospitalization for heart failure in patients with type-2 diabetes. AstraZeneca Press Release, 2019 Oct 21.
Dr. Como is a hospitalist and clinical instructor of medicine at the University of Utah, Salt Lake City.
Background: Dapagliflozin is a selective inhibitor of sodium-glucose transporter 2 (SGLT2) in the kidney; the drug blocks glucose reabsorption in the proximal tubule. It is taken once daily by mouth. An initial study sponsored by AstraZeneca was published January 2019 in the New England Journal of Medicine – “Dapagliflozin and cardiovascular outcomes in type 2 diabetes.” Until recently there was not an FDA-approved indication for the drug.
Study design: Randomized, double-blind, placebo-controlled trial.
Setting: 882 clinical sites in 33 countries.
Synopsis: The study randomized approximately 17,000 patients to receive either dapagliflozin or placebo in addition to any other diabetes treatments prescribed by their physician. This study demonstrated its primary safety outcome, which was that patients on dapagliflozin did not have any more major adverse cardiac events (MACE), compared with placebo. There were two primary efficacy outcomes. First, there was no change in MACE with dapagliflozin, compared with placebo. Second, and pertinent to this drug’s approval, was that dapagliflozin reduced risk of hospitalization for heart failure (HF) from 5.8% to 4.9%, compared to placebo; this includes both HF with both preserved and reduced ejection fractions.
Bottom line: Dapagliflozin now has an FDA-approved indication to reduce hospitalizations for HF in patients with type 2 diabetes. Based on this study, the number needed to treat with dapagliflozin is 111 patients to prevent one hospitalization for HF.
Citation: Farxiga approved in the US to reduce the risk of hospitalization for heart failure in patients with type-2 diabetes. AstraZeneca Press Release, 2019 Oct 21.
Dr. Como is a hospitalist and clinical instructor of medicine at the University of Utah, Salt Lake City.
Low concordance between troponin assays for ACS
Clinicians should be aware that the discordance between high-sensitivity cardiac troponin (hs-cTn) assays is significant enough that management recommendations may change, for example, for a patient assessed for suspected acute coronary syndrome (ACS) in one hospital and transferred to another that uses a different assay, according to a team of international researchers.
When hs-cTn concentrations were measured using the three Food and Drug Administration–approved assays, only 37.4% (384 of 1,027 samples) of blood samples were classified into the same analytical benchmark category.
“We didn’t expect such low concordance, to be honest, but I have to stress that this first assessment used just one-time blood testing and serial testing is what is more commonly recommended now,” said Júlia Karády, MD, from Massachusetts General Hospital and Harvard Medical School, both in Boston.
To see if concordance improved with serial testing, the researchers looked at the 242 patients for whom serial samples were available and saw concordance of management recommendations across assays rise to 74.8%.
“We tested the 0/2-hour algorithm and found that the overall agreement almost doubled, so I think that a very important message from our study is that serial testing improves the agreement between the assays in terms of clinical management and patient stratification,” said Dr. Karády.
Dr. Karády and colleagues published their findings in the Journal of the American College of Cardiology.
The researchers tested three assays referred to clinically as high-sensitivity assays: Elecsys 2010 platform (Roche Diagnostics); ARCHITECT i2000SR (Abbott Diagnostics); and hsVista (Siemens Diagnostics). All three have received FDA approval, starting with Elecsys in 2017.
The proportion of patients with similar management recommendations differed between the assays for both “rule-out” (87.2%, 73.1%, and 78.5% for Roche, Abbott, and Siemens, respectively) and “observe” (9.5%, 24%, and 17.8%; both P < .001). For the purposes of “rule-in,” no difference was noted (3.3%, 2.9%, and 3.7%).
“It’s important to note that this was a highly selected population of patients with an intermediate likelihood for ACS, not an all-comer population. This group comprises about 20% of the [emergency department] population and actually is the group we struggle with the most, which is hardest to diagnose because it excludes the very low– and very high–risk patients,” said Dr. Karády.
The patients included in this study all had suspected ACS and were enrolled in the ROMICAT-I and II trials.
Among 1,027 samples from 624 patients (mean age, 52.8 years; 39.4% women), samples were classified as below the limit of detection (LOD) in 56.3%, 10.4%, and 41.2% (P < .001) by Roche, Abbott, and Siemens, respectively.
The proportion of sample with a troponin measurement between LOD to the 99th percentile also differed significantly between the assays at 36.5%, 83.5%, and 52.6%, respectively (P < .001).
Only the proportion classified greater than 99th percentile did not differ (7.2%, 6.0%, and 6.2%; P = .114).
When the researchers looked at sex-specific difference, no differences were seen in rule-in numbers for men, but significant differences were seen for women.
“One possible explanation for this could be differences in the representation of men and women in the various reference populations used to develop the 99th percentile values for these assays,” suggested Dr. Karády.
They estimate around 30%-40% of U.S. centers are currently using high-sensitivity troponin assays and this number is “rapidly rising.”
The diagnostic algorithms developed for use with high-sensitivity assays, such as the 0/2-h algorithm, acknowledge differences in performance characteristics and recommend that assay-specific cut points be used for clinical decision-making rather than relying on generally applicable thresholds.
Joseph S. Alpert, MD, University of Arizona, Tucson, and coauthors of an accompanying editorial said the take-home message here is caveat emptor.
“First, ‘let the buyer (i.e., the clinician) beware’ when patients are transferred from one hospital to another, where different hs-cTn assays may be used,” they wrote. This is particularly true in women and in those with troponin levels in the “observe (gray zone)” clinical management recommendation.
Dr. Karády has received grant support from the Fulbright Visiting Researcher Grant and the Rosztoczy Foundation. One of the coauthors of the editorial comment consults or has consulted for most of the major diagnostic companies, including the manufacturers of the three assays tested in this study. Dr. Alpert disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Clinicians should be aware that the discordance between high-sensitivity cardiac troponin (hs-cTn) assays is significant enough that management recommendations may change, for example, for a patient assessed for suspected acute coronary syndrome (ACS) in one hospital and transferred to another that uses a different assay, according to a team of international researchers.
When hs-cTn concentrations were measured using the three Food and Drug Administration–approved assays, only 37.4% (384 of 1,027 samples) of blood samples were classified into the same analytical benchmark category.
“We didn’t expect such low concordance, to be honest, but I have to stress that this first assessment used just one-time blood testing and serial testing is what is more commonly recommended now,” said Júlia Karády, MD, from Massachusetts General Hospital and Harvard Medical School, both in Boston.
To see if concordance improved with serial testing, the researchers looked at the 242 patients for whom serial samples were available and saw concordance of management recommendations across assays rise to 74.8%.
“We tested the 0/2-hour algorithm and found that the overall agreement almost doubled, so I think that a very important message from our study is that serial testing improves the agreement between the assays in terms of clinical management and patient stratification,” said Dr. Karády.
Dr. Karády and colleagues published their findings in the Journal of the American College of Cardiology.
The researchers tested three assays referred to clinically as high-sensitivity assays: Elecsys 2010 platform (Roche Diagnostics); ARCHITECT i2000SR (Abbott Diagnostics); and hsVista (Siemens Diagnostics). All three have received FDA approval, starting with Elecsys in 2017.
The proportion of patients with similar management recommendations differed between the assays for both “rule-out” (87.2%, 73.1%, and 78.5% for Roche, Abbott, and Siemens, respectively) and “observe” (9.5%, 24%, and 17.8%; both P < .001). For the purposes of “rule-in,” no difference was noted (3.3%, 2.9%, and 3.7%).
“It’s important to note that this was a highly selected population of patients with an intermediate likelihood for ACS, not an all-comer population. This group comprises about 20% of the [emergency department] population and actually is the group we struggle with the most, which is hardest to diagnose because it excludes the very low– and very high–risk patients,” said Dr. Karády.
The patients included in this study all had suspected ACS and were enrolled in the ROMICAT-I and II trials.
Among 1,027 samples from 624 patients (mean age, 52.8 years; 39.4% women), samples were classified as below the limit of detection (LOD) in 56.3%, 10.4%, and 41.2% (P < .001) by Roche, Abbott, and Siemens, respectively.
The proportion of sample with a troponin measurement between LOD to the 99th percentile also differed significantly between the assays at 36.5%, 83.5%, and 52.6%, respectively (P < .001).
Only the proportion classified greater than 99th percentile did not differ (7.2%, 6.0%, and 6.2%; P = .114).
When the researchers looked at sex-specific difference, no differences were seen in rule-in numbers for men, but significant differences were seen for women.
“One possible explanation for this could be differences in the representation of men and women in the various reference populations used to develop the 99th percentile values for these assays,” suggested Dr. Karády.
They estimate around 30%-40% of U.S. centers are currently using high-sensitivity troponin assays and this number is “rapidly rising.”
The diagnostic algorithms developed for use with high-sensitivity assays, such as the 0/2-h algorithm, acknowledge differences in performance characteristics and recommend that assay-specific cut points be used for clinical decision-making rather than relying on generally applicable thresholds.
Joseph S. Alpert, MD, University of Arizona, Tucson, and coauthors of an accompanying editorial said the take-home message here is caveat emptor.
“First, ‘let the buyer (i.e., the clinician) beware’ when patients are transferred from one hospital to another, where different hs-cTn assays may be used,” they wrote. This is particularly true in women and in those with troponin levels in the “observe (gray zone)” clinical management recommendation.
Dr. Karády has received grant support from the Fulbright Visiting Researcher Grant and the Rosztoczy Foundation. One of the coauthors of the editorial comment consults or has consulted for most of the major diagnostic companies, including the manufacturers of the three assays tested in this study. Dr. Alpert disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Clinicians should be aware that the discordance between high-sensitivity cardiac troponin (hs-cTn) assays is significant enough that management recommendations may change, for example, for a patient assessed for suspected acute coronary syndrome (ACS) in one hospital and transferred to another that uses a different assay, according to a team of international researchers.
When hs-cTn concentrations were measured using the three Food and Drug Administration–approved assays, only 37.4% (384 of 1,027 samples) of blood samples were classified into the same analytical benchmark category.
“We didn’t expect such low concordance, to be honest, but I have to stress that this first assessment used just one-time blood testing and serial testing is what is more commonly recommended now,” said Júlia Karády, MD, from Massachusetts General Hospital and Harvard Medical School, both in Boston.
To see if concordance improved with serial testing, the researchers looked at the 242 patients for whom serial samples were available and saw concordance of management recommendations across assays rise to 74.8%.
“We tested the 0/2-hour algorithm and found that the overall agreement almost doubled, so I think that a very important message from our study is that serial testing improves the agreement between the assays in terms of clinical management and patient stratification,” said Dr. Karády.
Dr. Karády and colleagues published their findings in the Journal of the American College of Cardiology.
The researchers tested three assays referred to clinically as high-sensitivity assays: Elecsys 2010 platform (Roche Diagnostics); ARCHITECT i2000SR (Abbott Diagnostics); and hsVista (Siemens Diagnostics). All three have received FDA approval, starting with Elecsys in 2017.
The proportion of patients with similar management recommendations differed between the assays for both “rule-out” (87.2%, 73.1%, and 78.5% for Roche, Abbott, and Siemens, respectively) and “observe” (9.5%, 24%, and 17.8%; both P < .001). For the purposes of “rule-in,” no difference was noted (3.3%, 2.9%, and 3.7%).
“It’s important to note that this was a highly selected population of patients with an intermediate likelihood for ACS, not an all-comer population. This group comprises about 20% of the [emergency department] population and actually is the group we struggle with the most, which is hardest to diagnose because it excludes the very low– and very high–risk patients,” said Dr. Karády.
The patients included in this study all had suspected ACS and were enrolled in the ROMICAT-I and II trials.
Among 1,027 samples from 624 patients (mean age, 52.8 years; 39.4% women), samples were classified as below the limit of detection (LOD) in 56.3%, 10.4%, and 41.2% (P < .001) by Roche, Abbott, and Siemens, respectively.
The proportion of sample with a troponin measurement between LOD to the 99th percentile also differed significantly between the assays at 36.5%, 83.5%, and 52.6%, respectively (P < .001).
Only the proportion classified greater than 99th percentile did not differ (7.2%, 6.0%, and 6.2%; P = .114).
When the researchers looked at sex-specific difference, no differences were seen in rule-in numbers for men, but significant differences were seen for women.
“One possible explanation for this could be differences in the representation of men and women in the various reference populations used to develop the 99th percentile values for these assays,” suggested Dr. Karády.
They estimate around 30%-40% of U.S. centers are currently using high-sensitivity troponin assays and this number is “rapidly rising.”
The diagnostic algorithms developed for use with high-sensitivity assays, such as the 0/2-h algorithm, acknowledge differences in performance characteristics and recommend that assay-specific cut points be used for clinical decision-making rather than relying on generally applicable thresholds.
Joseph S. Alpert, MD, University of Arizona, Tucson, and coauthors of an accompanying editorial said the take-home message here is caveat emptor.
“First, ‘let the buyer (i.e., the clinician) beware’ when patients are transferred from one hospital to another, where different hs-cTn assays may be used,” they wrote. This is particularly true in women and in those with troponin levels in the “observe (gray zone)” clinical management recommendation.
Dr. Karády has received grant support from the Fulbright Visiting Researcher Grant and the Rosztoczy Foundation. One of the coauthors of the editorial comment consults or has consulted for most of the major diagnostic companies, including the manufacturers of the three assays tested in this study. Dr. Alpert disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
ApoB may better predict mortality risk in statin-treated patients
A new study shows apolipoprotein B (apoB) and non-HDL cholesterol – but not LDL cholesterol – are associated with increased risk for all-cause mortality and myocardial infarction in patients taking statins.
Moreover, apoB was a more accurate marker of all-cause mortality risk than non-HDL or LDL cholesterol and was more accurate at identifying MI risk than LDL cholesterol.
“Any patient that comes to a doctor for evaluation, if statin treatment is sufficient, the doctor should look not only at LDL cholesterol but HDL cholesterol and apoB, if its available – that is the take-home message,” senior author Børge Grønne Nordestgaard, MD, DMSC, University of Copenhagen, said in an interview.
The findings are very relevant to clinical practice because international guidelines focus on LDL cholesterol and “many doctors are brainwashed that that is the only thing they should look at, just to keep LDL cholesterol down,” he said. “I’ve worked for years with triglyceride lipoproteins, what I call remnant cholesterol, and I think that the risk is very high also when you have high remnant cholesterol.”
Previous work has shown that apoB and non-HDL cholesterol better reflect atherosclerotic cardiovascular disease risk than LDL cholesterol. This is the first study, however, to show that elevated apoB and non-HDL cholesterol are associated with a higher risk for all-cause death in statin-treated patients with low LDL cholesterol, Dr. Nordestgaard noted.
The investigators compared outcomes among 13,015 statin-treated participants in the Copenhagen General Population Study using median baseline values of 92 mg/dL for apoB, 3.1 mmol/L (120 mg/dL) for non-HDL cholesterol, and 2.3 mmol/L (89 mg/dL) for LDL cholesterol. Over a median follow-up of 8 years, there were 2,499 deaths and 537 MIs.
As reported in the Journal of the American College of Cardiology, discordant apoB above the median with LDL cholesterol below was associated with a 21% increased risk for all-cause mortality (hazard ratio, 1.21; 95% confidence interval, 1.07-1.36) and 49% increased risk for MI (HR, 1.49; 95% CI, 1.15-1.92), compared with concordant apoB and LDL cholesterol below the medians.
Similar results were found for discordant non-HDL cholesterol above the median with low LDL cholesterol for all-cause mortality (HR, 1.18; 95% CI, 1.02-1.36) and MI (1.78; 95% CI, 1.35-2.34).
No such associations with mortality or MI were observed when LDL cholesterol was above the median and apoB or non-HDL below.
Additional analyses showed that high apoB with low non-HDL cholesterol was associated with a higher risk for all-cause mortality (HR, 1.21; 95% CI, 1.03-1.41), whereas high non-HDL cholesterol with low apoB was associated with a lower risk (HR, 0.75; 95% CI, 0.62-0.92).
Current guidelines define apoB greater than 130 mg/dL as a risk modifier in patients not using statins but, the authors wrote, “based on our results, the threshold for apoB as a risk modifier in statin-treated patients should be closer to 92 mg/dL than to 130 mg/dL.”
In an accompanying editorial, Neil J. Stone, MD, and Donald Lloyd-Jones, MD, both from Northwestern University, Chicago, said that American and European guidelines acknowledge the usefulness of apoB and non-HDL cholesterol in their risk algorithms and as possible targets to indicate efficacy, but don’t give a strong recommendation for apoB to assess residual risk.
“This paper suggests that, in the next iteration, we’ve got to give a stronger thought to measuring apoB for residual risk in those with secondary prevention,” Dr. Stone, vice chair of the 2018 American Heart Association/ACC cholesterol guidelines, said in an interview.
“The whole part of the guidelines was not to focus on any one number but to focus on the clinical risk as a whole,” he said. “You can enlarge your understanding of the patient by looking at their non-HDL, which you have anyway, and in certain circumstances, for example, people with metabolic syndrome, diabetes, obesity, or high triglycerides, those people might very well benefit from an apoB to further understand their risk. This paper simply highlights that and, therefore, was very valuable.”
Dr. Stone and Dr. Lloyd-Jones, however, pointed out that statin use was self-reported and information was lacking on adherence, dose intensity, and the amount of LDL cholesterol lowering from baseline. LDL cholesterol levels were also above current recommendations for optimizing risk reduction. “If statin dosing and LDL [cholesterol] were not optimized already, then there may have been ‘room’ for non-HDL [cholesterol] and apoB to add value in understanding residual risk,” they wrote.
The editorialists suggested that sequential use, rather than regular use, of apoB and non-HDL cholesterol may be best and that incorporating this information may be particularly beneficial for patients with metabolic disorders and elevated triglycerides after statin therapy.
“Maybe this paper is a wake-up call that there are other markers out there that can tell you that you still have higher risk and need to tighten up lifestyle and maybe be more adherent,” Dr. Stone said. “I think this is a wonderful chance to say that preventive cardiology isn’t just ‘set it and forget it’.”
C. Noel Bairey Merz, MD, who coauthored the 2018 cholesterol guidelines, agreed there’s “an overexuberant focus on LDL [cholesterol] for residual risk” and highlighted a recent systematic review of statins, ezetimibe, and PCSK9 cardiovascular outcomes trials that showed very little gain from aggressively driving down LDL below 100 mg/dL, unless the patient is at extremely high risk.
“If I, as a treating cardiologist who spends a lot of time on lipids, had a patient on a high-intensity statin and they didn’t drop [their LDL cholesterol] 50% and I already had them going to cardiac rehab and they were already losing weight, would I measure apoB? Yeah, I might, to motivate them to do more or to take Vascepa,” she said.
“This study is a useful addition to a relatively important problem, which is residual risk, and really supports personalized or precision medicine,” added Bairey Merz, MD, Cedars-Sinai Medical Center, Los Angeles. “But now we have to do the work and do an intervention trial in these people and see whether these markers make a difference.”
The study was supported by Herlev and Gentofte Hospital’s Research Fund and the department of clinical biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital. Dr. Nordestgaard has had consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amarin, Amgen, Esperion, Kowa, Novartis, Novo Nordisk, and Silence Therapeutics. All other authors, Dr. Stone, and Dr. Lloyd-Jones reported no conflicts. Dr. Merz reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
A new study shows apolipoprotein B (apoB) and non-HDL cholesterol – but not LDL cholesterol – are associated with increased risk for all-cause mortality and myocardial infarction in patients taking statins.
Moreover, apoB was a more accurate marker of all-cause mortality risk than non-HDL or LDL cholesterol and was more accurate at identifying MI risk than LDL cholesterol.
“Any patient that comes to a doctor for evaluation, if statin treatment is sufficient, the doctor should look not only at LDL cholesterol but HDL cholesterol and apoB, if its available – that is the take-home message,” senior author Børge Grønne Nordestgaard, MD, DMSC, University of Copenhagen, said in an interview.
The findings are very relevant to clinical practice because international guidelines focus on LDL cholesterol and “many doctors are brainwashed that that is the only thing they should look at, just to keep LDL cholesterol down,” he said. “I’ve worked for years with triglyceride lipoproteins, what I call remnant cholesterol, and I think that the risk is very high also when you have high remnant cholesterol.”
Previous work has shown that apoB and non-HDL cholesterol better reflect atherosclerotic cardiovascular disease risk than LDL cholesterol. This is the first study, however, to show that elevated apoB and non-HDL cholesterol are associated with a higher risk for all-cause death in statin-treated patients with low LDL cholesterol, Dr. Nordestgaard noted.
The investigators compared outcomes among 13,015 statin-treated participants in the Copenhagen General Population Study using median baseline values of 92 mg/dL for apoB, 3.1 mmol/L (120 mg/dL) for non-HDL cholesterol, and 2.3 mmol/L (89 mg/dL) for LDL cholesterol. Over a median follow-up of 8 years, there were 2,499 deaths and 537 MIs.
As reported in the Journal of the American College of Cardiology, discordant apoB above the median with LDL cholesterol below was associated with a 21% increased risk for all-cause mortality (hazard ratio, 1.21; 95% confidence interval, 1.07-1.36) and 49% increased risk for MI (HR, 1.49; 95% CI, 1.15-1.92), compared with concordant apoB and LDL cholesterol below the medians.
Similar results were found for discordant non-HDL cholesterol above the median with low LDL cholesterol for all-cause mortality (HR, 1.18; 95% CI, 1.02-1.36) and MI (1.78; 95% CI, 1.35-2.34).
No such associations with mortality or MI were observed when LDL cholesterol was above the median and apoB or non-HDL below.
Additional analyses showed that high apoB with low non-HDL cholesterol was associated with a higher risk for all-cause mortality (HR, 1.21; 95% CI, 1.03-1.41), whereas high non-HDL cholesterol with low apoB was associated with a lower risk (HR, 0.75; 95% CI, 0.62-0.92).
Current guidelines define apoB greater than 130 mg/dL as a risk modifier in patients not using statins but, the authors wrote, “based on our results, the threshold for apoB as a risk modifier in statin-treated patients should be closer to 92 mg/dL than to 130 mg/dL.”
In an accompanying editorial, Neil J. Stone, MD, and Donald Lloyd-Jones, MD, both from Northwestern University, Chicago, said that American and European guidelines acknowledge the usefulness of apoB and non-HDL cholesterol in their risk algorithms and as possible targets to indicate efficacy, but don’t give a strong recommendation for apoB to assess residual risk.
“This paper suggests that, in the next iteration, we’ve got to give a stronger thought to measuring apoB for residual risk in those with secondary prevention,” Dr. Stone, vice chair of the 2018 American Heart Association/ACC cholesterol guidelines, said in an interview.
“The whole part of the guidelines was not to focus on any one number but to focus on the clinical risk as a whole,” he said. “You can enlarge your understanding of the patient by looking at their non-HDL, which you have anyway, and in certain circumstances, for example, people with metabolic syndrome, diabetes, obesity, or high triglycerides, those people might very well benefit from an apoB to further understand their risk. This paper simply highlights that and, therefore, was very valuable.”
Dr. Stone and Dr. Lloyd-Jones, however, pointed out that statin use was self-reported and information was lacking on adherence, dose intensity, and the amount of LDL cholesterol lowering from baseline. LDL cholesterol levels were also above current recommendations for optimizing risk reduction. “If statin dosing and LDL [cholesterol] were not optimized already, then there may have been ‘room’ for non-HDL [cholesterol] and apoB to add value in understanding residual risk,” they wrote.
The editorialists suggested that sequential use, rather than regular use, of apoB and non-HDL cholesterol may be best and that incorporating this information may be particularly beneficial for patients with metabolic disorders and elevated triglycerides after statin therapy.
“Maybe this paper is a wake-up call that there are other markers out there that can tell you that you still have higher risk and need to tighten up lifestyle and maybe be more adherent,” Dr. Stone said. “I think this is a wonderful chance to say that preventive cardiology isn’t just ‘set it and forget it’.”
C. Noel Bairey Merz, MD, who coauthored the 2018 cholesterol guidelines, agreed there’s “an overexuberant focus on LDL [cholesterol] for residual risk” and highlighted a recent systematic review of statins, ezetimibe, and PCSK9 cardiovascular outcomes trials that showed very little gain from aggressively driving down LDL below 100 mg/dL, unless the patient is at extremely high risk.
“If I, as a treating cardiologist who spends a lot of time on lipids, had a patient on a high-intensity statin and they didn’t drop [their LDL cholesterol] 50% and I already had them going to cardiac rehab and they were already losing weight, would I measure apoB? Yeah, I might, to motivate them to do more or to take Vascepa,” she said.
“This study is a useful addition to a relatively important problem, which is residual risk, and really supports personalized or precision medicine,” added Bairey Merz, MD, Cedars-Sinai Medical Center, Los Angeles. “But now we have to do the work and do an intervention trial in these people and see whether these markers make a difference.”
The study was supported by Herlev and Gentofte Hospital’s Research Fund and the department of clinical biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital. Dr. Nordestgaard has had consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amarin, Amgen, Esperion, Kowa, Novartis, Novo Nordisk, and Silence Therapeutics. All other authors, Dr. Stone, and Dr. Lloyd-Jones reported no conflicts. Dr. Merz reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
A new study shows apolipoprotein B (apoB) and non-HDL cholesterol – but not LDL cholesterol – are associated with increased risk for all-cause mortality and myocardial infarction in patients taking statins.
Moreover, apoB was a more accurate marker of all-cause mortality risk than non-HDL or LDL cholesterol and was more accurate at identifying MI risk than LDL cholesterol.
“Any patient that comes to a doctor for evaluation, if statin treatment is sufficient, the doctor should look not only at LDL cholesterol but HDL cholesterol and apoB, if its available – that is the take-home message,” senior author Børge Grønne Nordestgaard, MD, DMSC, University of Copenhagen, said in an interview.
The findings are very relevant to clinical practice because international guidelines focus on LDL cholesterol and “many doctors are brainwashed that that is the only thing they should look at, just to keep LDL cholesterol down,” he said. “I’ve worked for years with triglyceride lipoproteins, what I call remnant cholesterol, and I think that the risk is very high also when you have high remnant cholesterol.”
Previous work has shown that apoB and non-HDL cholesterol better reflect atherosclerotic cardiovascular disease risk than LDL cholesterol. This is the first study, however, to show that elevated apoB and non-HDL cholesterol are associated with a higher risk for all-cause death in statin-treated patients with low LDL cholesterol, Dr. Nordestgaard noted.
The investigators compared outcomes among 13,015 statin-treated participants in the Copenhagen General Population Study using median baseline values of 92 mg/dL for apoB, 3.1 mmol/L (120 mg/dL) for non-HDL cholesterol, and 2.3 mmol/L (89 mg/dL) for LDL cholesterol. Over a median follow-up of 8 years, there were 2,499 deaths and 537 MIs.
As reported in the Journal of the American College of Cardiology, discordant apoB above the median with LDL cholesterol below was associated with a 21% increased risk for all-cause mortality (hazard ratio, 1.21; 95% confidence interval, 1.07-1.36) and 49% increased risk for MI (HR, 1.49; 95% CI, 1.15-1.92), compared with concordant apoB and LDL cholesterol below the medians.
Similar results were found for discordant non-HDL cholesterol above the median with low LDL cholesterol for all-cause mortality (HR, 1.18; 95% CI, 1.02-1.36) and MI (1.78; 95% CI, 1.35-2.34).
No such associations with mortality or MI were observed when LDL cholesterol was above the median and apoB or non-HDL below.
Additional analyses showed that high apoB with low non-HDL cholesterol was associated with a higher risk for all-cause mortality (HR, 1.21; 95% CI, 1.03-1.41), whereas high non-HDL cholesterol with low apoB was associated with a lower risk (HR, 0.75; 95% CI, 0.62-0.92).
Current guidelines define apoB greater than 130 mg/dL as a risk modifier in patients not using statins but, the authors wrote, “based on our results, the threshold for apoB as a risk modifier in statin-treated patients should be closer to 92 mg/dL than to 130 mg/dL.”
In an accompanying editorial, Neil J. Stone, MD, and Donald Lloyd-Jones, MD, both from Northwestern University, Chicago, said that American and European guidelines acknowledge the usefulness of apoB and non-HDL cholesterol in their risk algorithms and as possible targets to indicate efficacy, but don’t give a strong recommendation for apoB to assess residual risk.
“This paper suggests that, in the next iteration, we’ve got to give a stronger thought to measuring apoB for residual risk in those with secondary prevention,” Dr. Stone, vice chair of the 2018 American Heart Association/ACC cholesterol guidelines, said in an interview.
“The whole part of the guidelines was not to focus on any one number but to focus on the clinical risk as a whole,” he said. “You can enlarge your understanding of the patient by looking at their non-HDL, which you have anyway, and in certain circumstances, for example, people with metabolic syndrome, diabetes, obesity, or high triglycerides, those people might very well benefit from an apoB to further understand their risk. This paper simply highlights that and, therefore, was very valuable.”
Dr. Stone and Dr. Lloyd-Jones, however, pointed out that statin use was self-reported and information was lacking on adherence, dose intensity, and the amount of LDL cholesterol lowering from baseline. LDL cholesterol levels were also above current recommendations for optimizing risk reduction. “If statin dosing and LDL [cholesterol] were not optimized already, then there may have been ‘room’ for non-HDL [cholesterol] and apoB to add value in understanding residual risk,” they wrote.
The editorialists suggested that sequential use, rather than regular use, of apoB and non-HDL cholesterol may be best and that incorporating this information may be particularly beneficial for patients with metabolic disorders and elevated triglycerides after statin therapy.
“Maybe this paper is a wake-up call that there are other markers out there that can tell you that you still have higher risk and need to tighten up lifestyle and maybe be more adherent,” Dr. Stone said. “I think this is a wonderful chance to say that preventive cardiology isn’t just ‘set it and forget it’.”
C. Noel Bairey Merz, MD, who coauthored the 2018 cholesterol guidelines, agreed there’s “an overexuberant focus on LDL [cholesterol] for residual risk” and highlighted a recent systematic review of statins, ezetimibe, and PCSK9 cardiovascular outcomes trials that showed very little gain from aggressively driving down LDL below 100 mg/dL, unless the patient is at extremely high risk.
“If I, as a treating cardiologist who spends a lot of time on lipids, had a patient on a high-intensity statin and they didn’t drop [their LDL cholesterol] 50% and I already had them going to cardiac rehab and they were already losing weight, would I measure apoB? Yeah, I might, to motivate them to do more or to take Vascepa,” she said.
“This study is a useful addition to a relatively important problem, which is residual risk, and really supports personalized or precision medicine,” added Bairey Merz, MD, Cedars-Sinai Medical Center, Los Angeles. “But now we have to do the work and do an intervention trial in these people and see whether these markers make a difference.”
The study was supported by Herlev and Gentofte Hospital’s Research Fund and the department of clinical biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital. Dr. Nordestgaard has had consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amarin, Amgen, Esperion, Kowa, Novartis, Novo Nordisk, and Silence Therapeutics. All other authors, Dr. Stone, and Dr. Lloyd-Jones reported no conflicts. Dr. Merz reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
Depression screening after ACS does not change outcomes
Background: Depression after ACS is common and is associated with increased mortality. Professional societies have recommended routine depression screening in these patients; however, this has not been consistently implemented because there is a lack of data to support routine screening.
Study design: Multicenter randomized clinical trial.
Setting: Four geographically diverse health systems in the United States.
Synopsis: In the CODIACS-QoL trial, 1,500 patients were randomized to three groups within 12 months of documented ACS: depression screening with notification to primary care and treatment, screening and notification to primary care, and no screening. Only 7.7% of the patients in the screen, notify, and treat group and 6.6% of screen and notify group screened positive for depression. There were no differences for the primary outcome of quality-adjusted life-years or the secondary outcome of depression-free days between groups. Additionally, there was no difference in mortality or patient-reported harms of screening between groups. The study excluded patients who already had a history of depression, psychiatric history, or other severe life-threatening medical conditions, which may have affected the outcomes.
Depression remains a substantial factor in coronary disease and quality of life; however, systematic depression screening appears to have limited population-level benefits.
Bottom line: Systematic depression screening with or without treatment offerings did not alter quality of life, depression-free days, or mortality in patients with ACS.
Citation: Kronish IM et al. Effect of depression screening after acute coronary syndrome on quality of life. JAMA Intern Med. 2020;180(1):45-53.
Dr. Ciarkowski is a hospitalist and clinical instructor of medicine at the University of Utah, Salt Lake City.
Background: Depression after ACS is common and is associated with increased mortality. Professional societies have recommended routine depression screening in these patients; however, this has not been consistently implemented because there is a lack of data to support routine screening.
Study design: Multicenter randomized clinical trial.
Setting: Four geographically diverse health systems in the United States.
Synopsis: In the CODIACS-QoL trial, 1,500 patients were randomized to three groups within 12 months of documented ACS: depression screening with notification to primary care and treatment, screening and notification to primary care, and no screening. Only 7.7% of the patients in the screen, notify, and treat group and 6.6% of screen and notify group screened positive for depression. There were no differences for the primary outcome of quality-adjusted life-years or the secondary outcome of depression-free days between groups. Additionally, there was no difference in mortality or patient-reported harms of screening between groups. The study excluded patients who already had a history of depression, psychiatric history, or other severe life-threatening medical conditions, which may have affected the outcomes.
Depression remains a substantial factor in coronary disease and quality of life; however, systematic depression screening appears to have limited population-level benefits.
Bottom line: Systematic depression screening with or without treatment offerings did not alter quality of life, depression-free days, or mortality in patients with ACS.
Citation: Kronish IM et al. Effect of depression screening after acute coronary syndrome on quality of life. JAMA Intern Med. 2020;180(1):45-53.
Dr. Ciarkowski is a hospitalist and clinical instructor of medicine at the University of Utah, Salt Lake City.
Background: Depression after ACS is common and is associated with increased mortality. Professional societies have recommended routine depression screening in these patients; however, this has not been consistently implemented because there is a lack of data to support routine screening.
Study design: Multicenter randomized clinical trial.
Setting: Four geographically diverse health systems in the United States.
Synopsis: In the CODIACS-QoL trial, 1,500 patients were randomized to three groups within 12 months of documented ACS: depression screening with notification to primary care and treatment, screening and notification to primary care, and no screening. Only 7.7% of the patients in the screen, notify, and treat group and 6.6% of screen and notify group screened positive for depression. There were no differences for the primary outcome of quality-adjusted life-years or the secondary outcome of depression-free days between groups. Additionally, there was no difference in mortality or patient-reported harms of screening between groups. The study excluded patients who already had a history of depression, psychiatric history, or other severe life-threatening medical conditions, which may have affected the outcomes.
Depression remains a substantial factor in coronary disease and quality of life; however, systematic depression screening appears to have limited population-level benefits.
Bottom line: Systematic depression screening with or without treatment offerings did not alter quality of life, depression-free days, or mortality in patients with ACS.
Citation: Kronish IM et al. Effect of depression screening after acute coronary syndrome on quality of life. JAMA Intern Med. 2020;180(1):45-53.
Dr. Ciarkowski is a hospitalist and clinical instructor of medicine at the University of Utah, Salt Lake City.
Direct transfer to angiography improves outcome in large-vessel stroke
in a new study.
Results of the ANGIO-CAT trial were presented at the International Stroke Conference sponsored by the American Heart Association.
The study involved patients suspected of having a large-vessel occlusion, as assessed in the prehospital setting by paramedics using the Rapid Arterial Occlusion Evaluation (RACE) score.
In his presentation, Manuel Requena, PhD, a neurologist and neurointerventionalist fellow at Vall d’Hebron Hospital, Barcelona, explained that, if patients were within 6 hours of symptom onset with a RACE scale score greater than 4, paramedics called ahead to a stroke neurologist, who met the patient directly at the hospital.
If on clinical examination the National Institutes of Health Stroke Scale (NIHSS) score was greater than 10, patients could be enrolled into the study. Upon enrollment, they were randomly assigned either to be taken directly to the angiography suite or to receive standard care.
Bypassing the emergency department
Dr. Requena noted that, at his center, patients who receive standard care are transferred to the CT imaging suite, where they are evaluated with noncontrast CT and CT angiography. CT perfusion is also performed if the treating physician deems it necessary.
If a large-vessel occlusion is confirmed, patients are then transferred to the angiography suite for endovascular treatment. He added that in many centers, patients are evaluated in the ED before undergoing CT scanning.
Patients in the direct angiography group received a “flat-panel” noncontrast CT in the angiography suite to rule out intracranial hemorrhage or a large, established infarct. The large-vessel occlusion would be confirmed by arteriography before the endovascular procedure was performed.
After CT scanning, patients received thrombolysis as recommended in the guidelines.
The current interim analysis includes the 174 patients who have been enrolled so far in the study. The median RACE score for these patients was 7, and the median NIHSS score was 17. Large-vessel occlusion was confirmed in 84% of patients, and 8% had an intracerebral hemorrhage.
Results showed that of the 147 patients who received endovascular therapy, puncture time was shorter for those who were taken directly to angiography (median, 18 min vs. 42 min), as was time to reperfusion (median, 57 min vs. 84 min).
The primary outcome was a shift analysis of the Modified Rankin Scale functional outcome scale at 90 days (odds of 1-point improvement or more). In the direct angiography group, the adjusted odds ratio for an improved functional outcome was 2.2 (95% confidence interval, 1.2-.1).
There were no significant differences in safety endpoints. There was a trend toward more procedural complications in those receiving endovascular therapy in the direct angiography group (8.1% vs. 2.7%; P = .6), but there was also a trend toward lower 90-day mortality in this group (20.2% vs. 32.9%; P = .07)
Dr. Requena reported no significant difference in safety outcomes among those with a hemorrhagic stroke.
“Our study is the first clinical trial that shows the superiority of direct transfer to an angiography suite,” said Dr. Requena. “Our findings were close to what we expected, and we were surprised that they occurred so early in the study. We trust that they will be confirmed in ongoing, multicenter, international trials.”
Stroke patients who were transferred directly to an angiography suite were also less likely to be dependent on assistance with daily activities than were those who received the current standard of care, Dr. Requena said. “More frequent and more rapid treatment can help improve outcomes for our stroke patients.”
A limitation of this study is that the hospital had extensive experience with immediate angiography, so findings may differ at hospitals or care centers with less angiography expertise or experience, Dr. Requena said.
He added that retrospective studies conducted in hospitals in the United States, Germany, and Switzerland show that this kind of protocol can be developed in any high-volume stroke center, although multicenter, international trials are needed.
The cost of speed
Commenting on the ANGIO-CAT study, Michael Hill, MD, a professor at the University of Calgary (Alta.), said the 27-minute improvement in door-to-reperfusion time achieved in the study was meaningful and correlates with the degree of improved outcomes observed. “So, the improvement in speed of treatment resulting in better outcomes makes sense,” he added.
He cautioned that this strategy would only be feasible in certain centers with selected patients and that cost will be a fundamental issue.
“If you identify patients at angiography, you risk having some patients with no target large-vessel occlusion,” Dr. Hill added. “The real question is, how many of these patients without a large-vessel occlusion can the system tolerate before it becomes uneconomical and not fruitful or harmful, given that groin puncture is not totally harmless?”
The moderator of the ISC news conference on the study, Mitchell Elkind, MD, professor of neurology at Columbia University, New York, who is also president of the American Stroke Association, said the study reflects the growing recognition of the importance of speed when treating stroke. “If we can shorten time to treatment using rapid evaluation and imaging protocols, this will help save brain,” he said.
Also commenting on the study, Louisa McCullough, MD, PhD, chief of neurology at Memorial Hermann Hospital–Texas Medical Center, Houston, who is the ISC meeting chair, said she thought the study would be relevant to the United States. “Speed is really of the essence. Whenever we can reduce delays, that will make a big difference to patients.”
Referring to this study on improving hospital systems, as well as a second study that was presented at the meeting that showed benefits from delivery of prehospital thrombolysis via a mobile stroke unit, Dr. McCullough added that “we need to set up models so we can get the best of both these worlds. These studies are really leading the way on how we can change the stroke systems of care.”
The study was funded by Vall d’Hebron Research Institute. Dr. Requena disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
in a new study.
Results of the ANGIO-CAT trial were presented at the International Stroke Conference sponsored by the American Heart Association.
The study involved patients suspected of having a large-vessel occlusion, as assessed in the prehospital setting by paramedics using the Rapid Arterial Occlusion Evaluation (RACE) score.
In his presentation, Manuel Requena, PhD, a neurologist and neurointerventionalist fellow at Vall d’Hebron Hospital, Barcelona, explained that, if patients were within 6 hours of symptom onset with a RACE scale score greater than 4, paramedics called ahead to a stroke neurologist, who met the patient directly at the hospital.
If on clinical examination the National Institutes of Health Stroke Scale (NIHSS) score was greater than 10, patients could be enrolled into the study. Upon enrollment, they were randomly assigned either to be taken directly to the angiography suite or to receive standard care.
Bypassing the emergency department
Dr. Requena noted that, at his center, patients who receive standard care are transferred to the CT imaging suite, where they are evaluated with noncontrast CT and CT angiography. CT perfusion is also performed if the treating physician deems it necessary.
If a large-vessel occlusion is confirmed, patients are then transferred to the angiography suite for endovascular treatment. He added that in many centers, patients are evaluated in the ED before undergoing CT scanning.
Patients in the direct angiography group received a “flat-panel” noncontrast CT in the angiography suite to rule out intracranial hemorrhage or a large, established infarct. The large-vessel occlusion would be confirmed by arteriography before the endovascular procedure was performed.
After CT scanning, patients received thrombolysis as recommended in the guidelines.
The current interim analysis includes the 174 patients who have been enrolled so far in the study. The median RACE score for these patients was 7, and the median NIHSS score was 17. Large-vessel occlusion was confirmed in 84% of patients, and 8% had an intracerebral hemorrhage.
Results showed that of the 147 patients who received endovascular therapy, puncture time was shorter for those who were taken directly to angiography (median, 18 min vs. 42 min), as was time to reperfusion (median, 57 min vs. 84 min).
The primary outcome was a shift analysis of the Modified Rankin Scale functional outcome scale at 90 days (odds of 1-point improvement or more). In the direct angiography group, the adjusted odds ratio for an improved functional outcome was 2.2 (95% confidence interval, 1.2-.1).
There were no significant differences in safety endpoints. There was a trend toward more procedural complications in those receiving endovascular therapy in the direct angiography group (8.1% vs. 2.7%; P = .6), but there was also a trend toward lower 90-day mortality in this group (20.2% vs. 32.9%; P = .07)
Dr. Requena reported no significant difference in safety outcomes among those with a hemorrhagic stroke.
“Our study is the first clinical trial that shows the superiority of direct transfer to an angiography suite,” said Dr. Requena. “Our findings were close to what we expected, and we were surprised that they occurred so early in the study. We trust that they will be confirmed in ongoing, multicenter, international trials.”
Stroke patients who were transferred directly to an angiography suite were also less likely to be dependent on assistance with daily activities than were those who received the current standard of care, Dr. Requena said. “More frequent and more rapid treatment can help improve outcomes for our stroke patients.”
A limitation of this study is that the hospital had extensive experience with immediate angiography, so findings may differ at hospitals or care centers with less angiography expertise or experience, Dr. Requena said.
He added that retrospective studies conducted in hospitals in the United States, Germany, and Switzerland show that this kind of protocol can be developed in any high-volume stroke center, although multicenter, international trials are needed.
The cost of speed
Commenting on the ANGIO-CAT study, Michael Hill, MD, a professor at the University of Calgary (Alta.), said the 27-minute improvement in door-to-reperfusion time achieved in the study was meaningful and correlates with the degree of improved outcomes observed. “So, the improvement in speed of treatment resulting in better outcomes makes sense,” he added.
He cautioned that this strategy would only be feasible in certain centers with selected patients and that cost will be a fundamental issue.
“If you identify patients at angiography, you risk having some patients with no target large-vessel occlusion,” Dr. Hill added. “The real question is, how many of these patients without a large-vessel occlusion can the system tolerate before it becomes uneconomical and not fruitful or harmful, given that groin puncture is not totally harmless?”
The moderator of the ISC news conference on the study, Mitchell Elkind, MD, professor of neurology at Columbia University, New York, who is also president of the American Stroke Association, said the study reflects the growing recognition of the importance of speed when treating stroke. “If we can shorten time to treatment using rapid evaluation and imaging protocols, this will help save brain,” he said.
Also commenting on the study, Louisa McCullough, MD, PhD, chief of neurology at Memorial Hermann Hospital–Texas Medical Center, Houston, who is the ISC meeting chair, said she thought the study would be relevant to the United States. “Speed is really of the essence. Whenever we can reduce delays, that will make a big difference to patients.”
Referring to this study on improving hospital systems, as well as a second study that was presented at the meeting that showed benefits from delivery of prehospital thrombolysis via a mobile stroke unit, Dr. McCullough added that “we need to set up models so we can get the best of both these worlds. These studies are really leading the way on how we can change the stroke systems of care.”
The study was funded by Vall d’Hebron Research Institute. Dr. Requena disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
in a new study.
Results of the ANGIO-CAT trial were presented at the International Stroke Conference sponsored by the American Heart Association.
The study involved patients suspected of having a large-vessel occlusion, as assessed in the prehospital setting by paramedics using the Rapid Arterial Occlusion Evaluation (RACE) score.
In his presentation, Manuel Requena, PhD, a neurologist and neurointerventionalist fellow at Vall d’Hebron Hospital, Barcelona, explained that, if patients were within 6 hours of symptom onset with a RACE scale score greater than 4, paramedics called ahead to a stroke neurologist, who met the patient directly at the hospital.
If on clinical examination the National Institutes of Health Stroke Scale (NIHSS) score was greater than 10, patients could be enrolled into the study. Upon enrollment, they were randomly assigned either to be taken directly to the angiography suite or to receive standard care.
Bypassing the emergency department
Dr. Requena noted that, at his center, patients who receive standard care are transferred to the CT imaging suite, where they are evaluated with noncontrast CT and CT angiography. CT perfusion is also performed if the treating physician deems it necessary.
If a large-vessel occlusion is confirmed, patients are then transferred to the angiography suite for endovascular treatment. He added that in many centers, patients are evaluated in the ED before undergoing CT scanning.
Patients in the direct angiography group received a “flat-panel” noncontrast CT in the angiography suite to rule out intracranial hemorrhage or a large, established infarct. The large-vessel occlusion would be confirmed by arteriography before the endovascular procedure was performed.
After CT scanning, patients received thrombolysis as recommended in the guidelines.
The current interim analysis includes the 174 patients who have been enrolled so far in the study. The median RACE score for these patients was 7, and the median NIHSS score was 17. Large-vessel occlusion was confirmed in 84% of patients, and 8% had an intracerebral hemorrhage.
Results showed that of the 147 patients who received endovascular therapy, puncture time was shorter for those who were taken directly to angiography (median, 18 min vs. 42 min), as was time to reperfusion (median, 57 min vs. 84 min).
The primary outcome was a shift analysis of the Modified Rankin Scale functional outcome scale at 90 days (odds of 1-point improvement or more). In the direct angiography group, the adjusted odds ratio for an improved functional outcome was 2.2 (95% confidence interval, 1.2-.1).
There were no significant differences in safety endpoints. There was a trend toward more procedural complications in those receiving endovascular therapy in the direct angiography group (8.1% vs. 2.7%; P = .6), but there was also a trend toward lower 90-day mortality in this group (20.2% vs. 32.9%; P = .07)
Dr. Requena reported no significant difference in safety outcomes among those with a hemorrhagic stroke.
“Our study is the first clinical trial that shows the superiority of direct transfer to an angiography suite,” said Dr. Requena. “Our findings were close to what we expected, and we were surprised that they occurred so early in the study. We trust that they will be confirmed in ongoing, multicenter, international trials.”
Stroke patients who were transferred directly to an angiography suite were also less likely to be dependent on assistance with daily activities than were those who received the current standard of care, Dr. Requena said. “More frequent and more rapid treatment can help improve outcomes for our stroke patients.”
A limitation of this study is that the hospital had extensive experience with immediate angiography, so findings may differ at hospitals or care centers with less angiography expertise or experience, Dr. Requena said.
He added that retrospective studies conducted in hospitals in the United States, Germany, and Switzerland show that this kind of protocol can be developed in any high-volume stroke center, although multicenter, international trials are needed.
The cost of speed
Commenting on the ANGIO-CAT study, Michael Hill, MD, a professor at the University of Calgary (Alta.), said the 27-minute improvement in door-to-reperfusion time achieved in the study was meaningful and correlates with the degree of improved outcomes observed. “So, the improvement in speed of treatment resulting in better outcomes makes sense,” he added.
He cautioned that this strategy would only be feasible in certain centers with selected patients and that cost will be a fundamental issue.
“If you identify patients at angiography, you risk having some patients with no target large-vessel occlusion,” Dr. Hill added. “The real question is, how many of these patients without a large-vessel occlusion can the system tolerate before it becomes uneconomical and not fruitful or harmful, given that groin puncture is not totally harmless?”
The moderator of the ISC news conference on the study, Mitchell Elkind, MD, professor of neurology at Columbia University, New York, who is also president of the American Stroke Association, said the study reflects the growing recognition of the importance of speed when treating stroke. “If we can shorten time to treatment using rapid evaluation and imaging protocols, this will help save brain,” he said.
Also commenting on the study, Louisa McCullough, MD, PhD, chief of neurology at Memorial Hermann Hospital–Texas Medical Center, Houston, who is the ISC meeting chair, said she thought the study would be relevant to the United States. “Speed is really of the essence. Whenever we can reduce delays, that will make a big difference to patients.”
Referring to this study on improving hospital systems, as well as a second study that was presented at the meeting that showed benefits from delivery of prehospital thrombolysis via a mobile stroke unit, Dr. McCullough added that “we need to set up models so we can get the best of both these worlds. These studies are really leading the way on how we can change the stroke systems of care.”
The study was funded by Vall d’Hebron Research Institute. Dr. Requena disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ISC 2021
Blood pressure meds tied to increased schizophrenia risk
ACE inhibitors may be associated with an increased risk for schizophrenia and may affect psychiatric symptoms, new research suggests.
Investigators found individuals who carry a genetic variant associated with lower levels of the ACE gene and protein have increased liability to schizophrenia, suggesting that drugs that lower ACE levels or activity may do the same.
“Our findings warrant further investigation into the role of ACE in schizophrenia and closer monitoring by clinicians of individuals, especially those with schizophrenia, who may be on medication that lower ACE activity, such as ACE inhibitors,” Sonia Shah, PhD, Institute for Biomedical Sciences, University of Queensland, Brisbane, Australia, said in an interview.
The study was published online March 10, 2021, in JAMA Psychiatry.
Antihypertensives and mental illness
Hypertension is common in patients with psychiatric disorders and observational studies have reported associations between antihypertensive medication and these disorders, although the findings have been mixed.
Dr. Shah and colleagues estimated the potential of different antihypertensive drug classes on schizophrenia, bipolar disorder, and major depressive disorder.
In a two-sample Mendelian randomization study, they evaluated ties between a single-nucleotide variant and drug-target gene expression derived from expression quantitative trait loci data in blood (sample 1) and the SNV disease association from published case-control, genomewide association studies (sample 2).
The analyses included 40,675 patients with schizophrenia and 64,643 controls; 20,352 with bipolar disorder and 31,358 controls; and 135,458 with major depressive disorder and 344,901 controls.
The major finding was that a one standard deviation–lower expression of the ACE gene in blood was associated with lower systolic blood pressure of 4.0 mm Hg (95% confidence interval, 2.7-5.3), but also an increased risk of schizophrenia (odds ratio, 1.75; 95% CI, 1.28-2.38).
Could ACE inhibitors worsen symptoms or trigger episodes?
In their article, the researchers noted that, in most patients, onset of schizophrenia occurs in late adolescence or early adult life, ruling out ACE inhibitor treatment as a potential causal factor for most cases.
“However, if lower ACE levels play a causal role for schizophrenia risk, it would be reasonable to hypothesize that further lowering of ACE activity in existing patients could worsen symptoms or trigger a new episode,” they wrote.
Dr. Shah emphasized that evidence from genetic analyses alone is “not sufficient to justify changes in prescription guidelines.”
“Patients should not stop taking these medications if they are effective at controlling their blood pressure and they don’t suffer any adverse effects. But it would be reasonable to encourage greater pharmacovigilance,” she said in an interview.
“One way in which we are hoping to follow up these findings,” said Dr. Shah, “is to access electronic health record data for millions of individuals to investigate if there is evidence of increased rates of psychotic episodes in individuals who use ACE inhibitors, compared to other classes of blood pressure–lowering medication.”
Caution warranted
Reached for comment, Timothy Sullivan, MD, chair of psychiatry and behavioral sciences at Staten Island University Hospital in New York, noted that this is an “extremely complicated” study and urged caution in interpreting the results.
“Since most people develop schizophrenia earlier in life, before they usually develop problems with blood pressure, it’s not so much that these drugs might cause schizophrenia,” Dr. Sullivan said.
“But because of their effects on this particular gene, there’s a possibility that they might worsen symptoms or in somebody with borderline risk might cause them to develop symptoms later in life. This may apply to a relatively small number of people who develop symptoms of schizophrenia in their 40s and beyond,” he added.
That’s where “pharmacovigilance” comes into play, Dr. Sullivan said. “In other words, that they otherwise wouldn’t experience?”
Support for the study was provided by the National Health and Medical Research Council (Australia) and U.S. National Institute for Mental Health. Dr. Shah and Dr. Sullivan disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
ACE inhibitors may be associated with an increased risk for schizophrenia and may affect psychiatric symptoms, new research suggests.
Investigators found individuals who carry a genetic variant associated with lower levels of the ACE gene and protein have increased liability to schizophrenia, suggesting that drugs that lower ACE levels or activity may do the same.
“Our findings warrant further investigation into the role of ACE in schizophrenia and closer monitoring by clinicians of individuals, especially those with schizophrenia, who may be on medication that lower ACE activity, such as ACE inhibitors,” Sonia Shah, PhD, Institute for Biomedical Sciences, University of Queensland, Brisbane, Australia, said in an interview.
The study was published online March 10, 2021, in JAMA Psychiatry.
Antihypertensives and mental illness
Hypertension is common in patients with psychiatric disorders and observational studies have reported associations between antihypertensive medication and these disorders, although the findings have been mixed.
Dr. Shah and colleagues estimated the potential of different antihypertensive drug classes on schizophrenia, bipolar disorder, and major depressive disorder.
In a two-sample Mendelian randomization study, they evaluated ties between a single-nucleotide variant and drug-target gene expression derived from expression quantitative trait loci data in blood (sample 1) and the SNV disease association from published case-control, genomewide association studies (sample 2).
The analyses included 40,675 patients with schizophrenia and 64,643 controls; 20,352 with bipolar disorder and 31,358 controls; and 135,458 with major depressive disorder and 344,901 controls.
The major finding was that a one standard deviation–lower expression of the ACE gene in blood was associated with lower systolic blood pressure of 4.0 mm Hg (95% confidence interval, 2.7-5.3), but also an increased risk of schizophrenia (odds ratio, 1.75; 95% CI, 1.28-2.38).
Could ACE inhibitors worsen symptoms or trigger episodes?
In their article, the researchers noted that, in most patients, onset of schizophrenia occurs in late adolescence or early adult life, ruling out ACE inhibitor treatment as a potential causal factor for most cases.
“However, if lower ACE levels play a causal role for schizophrenia risk, it would be reasonable to hypothesize that further lowering of ACE activity in existing patients could worsen symptoms or trigger a new episode,” they wrote.
Dr. Shah emphasized that evidence from genetic analyses alone is “not sufficient to justify changes in prescription guidelines.”
“Patients should not stop taking these medications if they are effective at controlling their blood pressure and they don’t suffer any adverse effects. But it would be reasonable to encourage greater pharmacovigilance,” she said in an interview.
“One way in which we are hoping to follow up these findings,” said Dr. Shah, “is to access electronic health record data for millions of individuals to investigate if there is evidence of increased rates of psychotic episodes in individuals who use ACE inhibitors, compared to other classes of blood pressure–lowering medication.”
Caution warranted
Reached for comment, Timothy Sullivan, MD, chair of psychiatry and behavioral sciences at Staten Island University Hospital in New York, noted that this is an “extremely complicated” study and urged caution in interpreting the results.
“Since most people develop schizophrenia earlier in life, before they usually develop problems with blood pressure, it’s not so much that these drugs might cause schizophrenia,” Dr. Sullivan said.
“But because of their effects on this particular gene, there’s a possibility that they might worsen symptoms or in somebody with borderline risk might cause them to develop symptoms later in life. This may apply to a relatively small number of people who develop symptoms of schizophrenia in their 40s and beyond,” he added.
That’s where “pharmacovigilance” comes into play, Dr. Sullivan said. “In other words, that they otherwise wouldn’t experience?”
Support for the study was provided by the National Health and Medical Research Council (Australia) and U.S. National Institute for Mental Health. Dr. Shah and Dr. Sullivan disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
ACE inhibitors may be associated with an increased risk for schizophrenia and may affect psychiatric symptoms, new research suggests.
Investigators found individuals who carry a genetic variant associated with lower levels of the ACE gene and protein have increased liability to schizophrenia, suggesting that drugs that lower ACE levels or activity may do the same.
“Our findings warrant further investigation into the role of ACE in schizophrenia and closer monitoring by clinicians of individuals, especially those with schizophrenia, who may be on medication that lower ACE activity, such as ACE inhibitors,” Sonia Shah, PhD, Institute for Biomedical Sciences, University of Queensland, Brisbane, Australia, said in an interview.
The study was published online March 10, 2021, in JAMA Psychiatry.
Antihypertensives and mental illness
Hypertension is common in patients with psychiatric disorders and observational studies have reported associations between antihypertensive medication and these disorders, although the findings have been mixed.
Dr. Shah and colleagues estimated the potential of different antihypertensive drug classes on schizophrenia, bipolar disorder, and major depressive disorder.
In a two-sample Mendelian randomization study, they evaluated ties between a single-nucleotide variant and drug-target gene expression derived from expression quantitative trait loci data in blood (sample 1) and the SNV disease association from published case-control, genomewide association studies (sample 2).
The analyses included 40,675 patients with schizophrenia and 64,643 controls; 20,352 with bipolar disorder and 31,358 controls; and 135,458 with major depressive disorder and 344,901 controls.
The major finding was that a one standard deviation–lower expression of the ACE gene in blood was associated with lower systolic blood pressure of 4.0 mm Hg (95% confidence interval, 2.7-5.3), but also an increased risk of schizophrenia (odds ratio, 1.75; 95% CI, 1.28-2.38).
Could ACE inhibitors worsen symptoms or trigger episodes?
In their article, the researchers noted that, in most patients, onset of schizophrenia occurs in late adolescence or early adult life, ruling out ACE inhibitor treatment as a potential causal factor for most cases.
“However, if lower ACE levels play a causal role for schizophrenia risk, it would be reasonable to hypothesize that further lowering of ACE activity in existing patients could worsen symptoms or trigger a new episode,” they wrote.
Dr. Shah emphasized that evidence from genetic analyses alone is “not sufficient to justify changes in prescription guidelines.”
“Patients should not stop taking these medications if they are effective at controlling their blood pressure and they don’t suffer any adverse effects. But it would be reasonable to encourage greater pharmacovigilance,” she said in an interview.
“One way in which we are hoping to follow up these findings,” said Dr. Shah, “is to access electronic health record data for millions of individuals to investigate if there is evidence of increased rates of psychotic episodes in individuals who use ACE inhibitors, compared to other classes of blood pressure–lowering medication.”
Caution warranted
Reached for comment, Timothy Sullivan, MD, chair of psychiatry and behavioral sciences at Staten Island University Hospital in New York, noted that this is an “extremely complicated” study and urged caution in interpreting the results.
“Since most people develop schizophrenia earlier in life, before they usually develop problems with blood pressure, it’s not so much that these drugs might cause schizophrenia,” Dr. Sullivan said.
“But because of their effects on this particular gene, there’s a possibility that they might worsen symptoms or in somebody with borderline risk might cause them to develop symptoms later in life. This may apply to a relatively small number of people who develop symptoms of schizophrenia in their 40s and beyond,” he added.
That’s where “pharmacovigilance” comes into play, Dr. Sullivan said. “In other words, that they otherwise wouldn’t experience?”
Support for the study was provided by the National Health and Medical Research Council (Australia) and U.S. National Institute for Mental Health. Dr. Shah and Dr. Sullivan disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Ultraprocessed foods, many marketed as healthy, raise CVD risk
Eating ultraprocessed foods poses a significant risk to cardiovascular and coronary heart health, according to prospective data from about 3,000 people in the Framingham Offspring Cohort, the second generation of participants in the Framingham Heart Study.
Each regular, daily serving of ultraprocessed food was linked with significant elevations of 5%-9% in the relative rates of “hard” cardiovascular disease (CVD) events, hard coronary heart disease (CHD) events, overall CVD events, and CVD death, after adjustments for numerous potential confounders including energy intake, body mass index, waist circumference, and blood pressure, Filippa Juul, PhD, and associates wrote in a report published in the Journal of the American College of Cardiology.
“Consumption of ultraprocessed foods makes up over half of the daily calories in the average American diet and are increasingly consumed worldwide. As poor diet is a major modifiable risk factor for heart disease, it represents a critical target in prevention efforts,” said Dr. Juul, a nutritional epidemiologist at New York University, in a statement released by the American College of Cardiology.
“Our findings add to a growing body of evidence suggesting cardiovascular benefits of limiting ultraprocessed foods. Ultraprocessed foods are ubiquitous and include many foods that are marketed as healthy, such as protein bars, breakfast cereals, and most industrially produced breads,” she added. Other commonplace members of the ultraprocessed food group include carbonated soft drinks, packaged snacks, candies, sausages, margarines, and energy drinks. The concept of ultraprocessed foods as a distinct, wide-ranging, and dangerous food category first appeared in 2010, and then received an update from a United Nations panel in 2019 as what’s now called the NOVA classification system.
Ultraprocessed foods fly under the radar
“Although cardiovascular guidelines emphasize consuming minimally processed foods, such as fruits, vegetables, whole grains, and nuts, they give less attention to the importance of minimizing ultraprocessed food,” wrote Robert J. Ostfeld, MD, and Kathleen E. Allen, MS, in an editorial that accompanied the new report. This reduced attention may be because of a “paucity of studies examining the association cardiovascular outcomes and ultraprocessed foods.”
The new evidence demands new policies, educational efforts, and labeling changes, suggested Dr. Ostfeld, director of preventive cardiology at Montefiore Health System in New York, and Ms. Allen, a dietitian at the Geisel School of Medicine at Dartmouth, Hanover, N.H. “The goal should be to make the unhealthy choice the hard choice and the healthy choice the easy choice.”
The new analysis used data collected from people enrolled the Framingham Offspring Cohort, with their clinical metrics and diet information collected during 1991-1995 serving as their baseline. After excluding participants with prevalent CVD at baseline and those with incomplete follow-up of CVD events, the researchers had a cohort of 3,003 adults with an average follow-up of 18 years. At baseline, the cohort averaged 54 years of age; 55% were women, their average body mass index was 27.3 kg/m2, and about 6% had diabetes. They reported eating, on average, 7.5 servings of ultraprocessed food daily.
During follow-up, the cohort tallied 648 incident CVD events, including 251 hard CVD events (coronary death, MI, or stroke) and 163 hard CHD events (coronary death or MI), and 713 total deaths including 108 CVD deaths. Other CVD events recorded but not considered hard included heart failure, intermittent claudication, and transient ischemic attack.
In a multivariate-adjusted analysis, each average daily portion of ultraprocessed food was linked with an significant 7% relative increase in the incidence of a hard CVD event, compared with participants who ate fewer ultraprocessed food portions, and a 9% relative increase in the rate of hard CHD events, the study’s two prespecified primary outcomes. The researchers also found that each ultraprocessed serving significantly was associated with a 5% relative increased rate of total CVD events, and a 9% relative rise in CVD deaths. The analysis showed no significant association between total mortality and ultraprocessed food intake. (Average follow-up for the mortality analyses was 20 years.)
The authors also reported endpoint associations with intake of specific types of ultraprocessed foods, and found significantly increased associations specifically for portions of bread, ultraprocessed meat, salty snacks, and low-calorie soft drinks.
Convenient, omnipresent, and affordable
The authors acknowledged that the associations they found need examination in ethnically diverse populations, but nonetheless the findings “suggest the need for increased efforts to implement population-wide strategies” to lower consumption of ultraprocessed foods. “Given the convenience, omnipresence, and affordability of ultraprocessed foods, careful nutrition counseling is needed to design individualized, patient-centered, heart-healthy diets,” they concluded.
“Population-wide strategies such as taxation on sugar-sweetened beverages and other ultraprocessed foods and recommendations regarding processing levels in national dietary guidelines are needed to reduce the intake of ultraprocessed foods,” added Dr. Juul in her statement. “Of course, we must also implement policies that increase the availability, accessibility, and affordability of nutritious, minimally processed foods, especially in disadvantaged populations. At the clinical level, there is a need for increased commitment to individualized nutrition counseling for adopting sustainable heart-healthy diets.”
The study had no commercial funding. Dr. Juul and coauthors, Dr. Ostfeld, and Ms. Allen had no disclosures.
Eating ultraprocessed foods poses a significant risk to cardiovascular and coronary heart health, according to prospective data from about 3,000 people in the Framingham Offspring Cohort, the second generation of participants in the Framingham Heart Study.
Each regular, daily serving of ultraprocessed food was linked with significant elevations of 5%-9% in the relative rates of “hard” cardiovascular disease (CVD) events, hard coronary heart disease (CHD) events, overall CVD events, and CVD death, after adjustments for numerous potential confounders including energy intake, body mass index, waist circumference, and blood pressure, Filippa Juul, PhD, and associates wrote in a report published in the Journal of the American College of Cardiology.
“Consumption of ultraprocessed foods makes up over half of the daily calories in the average American diet and are increasingly consumed worldwide. As poor diet is a major modifiable risk factor for heart disease, it represents a critical target in prevention efforts,” said Dr. Juul, a nutritional epidemiologist at New York University, in a statement released by the American College of Cardiology.
“Our findings add to a growing body of evidence suggesting cardiovascular benefits of limiting ultraprocessed foods. Ultraprocessed foods are ubiquitous and include many foods that are marketed as healthy, such as protein bars, breakfast cereals, and most industrially produced breads,” she added. Other commonplace members of the ultraprocessed food group include carbonated soft drinks, packaged snacks, candies, sausages, margarines, and energy drinks. The concept of ultraprocessed foods as a distinct, wide-ranging, and dangerous food category first appeared in 2010, and then received an update from a United Nations panel in 2019 as what’s now called the NOVA classification system.
Ultraprocessed foods fly under the radar
“Although cardiovascular guidelines emphasize consuming minimally processed foods, such as fruits, vegetables, whole grains, and nuts, they give less attention to the importance of minimizing ultraprocessed food,” wrote Robert J. Ostfeld, MD, and Kathleen E. Allen, MS, in an editorial that accompanied the new report. This reduced attention may be because of a “paucity of studies examining the association cardiovascular outcomes and ultraprocessed foods.”
The new evidence demands new policies, educational efforts, and labeling changes, suggested Dr. Ostfeld, director of preventive cardiology at Montefiore Health System in New York, and Ms. Allen, a dietitian at the Geisel School of Medicine at Dartmouth, Hanover, N.H. “The goal should be to make the unhealthy choice the hard choice and the healthy choice the easy choice.”
The new analysis used data collected from people enrolled the Framingham Offspring Cohort, with their clinical metrics and diet information collected during 1991-1995 serving as their baseline. After excluding participants with prevalent CVD at baseline and those with incomplete follow-up of CVD events, the researchers had a cohort of 3,003 adults with an average follow-up of 18 years. At baseline, the cohort averaged 54 years of age; 55% were women, their average body mass index was 27.3 kg/m2, and about 6% had diabetes. They reported eating, on average, 7.5 servings of ultraprocessed food daily.
During follow-up, the cohort tallied 648 incident CVD events, including 251 hard CVD events (coronary death, MI, or stroke) and 163 hard CHD events (coronary death or MI), and 713 total deaths including 108 CVD deaths. Other CVD events recorded but not considered hard included heart failure, intermittent claudication, and transient ischemic attack.
In a multivariate-adjusted analysis, each average daily portion of ultraprocessed food was linked with an significant 7% relative increase in the incidence of a hard CVD event, compared with participants who ate fewer ultraprocessed food portions, and a 9% relative increase in the rate of hard CHD events, the study’s two prespecified primary outcomes. The researchers also found that each ultraprocessed serving significantly was associated with a 5% relative increased rate of total CVD events, and a 9% relative rise in CVD deaths. The analysis showed no significant association between total mortality and ultraprocessed food intake. (Average follow-up for the mortality analyses was 20 years.)
The authors also reported endpoint associations with intake of specific types of ultraprocessed foods, and found significantly increased associations specifically for portions of bread, ultraprocessed meat, salty snacks, and low-calorie soft drinks.
Convenient, omnipresent, and affordable
The authors acknowledged that the associations they found need examination in ethnically diverse populations, but nonetheless the findings “suggest the need for increased efforts to implement population-wide strategies” to lower consumption of ultraprocessed foods. “Given the convenience, omnipresence, and affordability of ultraprocessed foods, careful nutrition counseling is needed to design individualized, patient-centered, heart-healthy diets,” they concluded.
“Population-wide strategies such as taxation on sugar-sweetened beverages and other ultraprocessed foods and recommendations regarding processing levels in national dietary guidelines are needed to reduce the intake of ultraprocessed foods,” added Dr. Juul in her statement. “Of course, we must also implement policies that increase the availability, accessibility, and affordability of nutritious, minimally processed foods, especially in disadvantaged populations. At the clinical level, there is a need for increased commitment to individualized nutrition counseling for adopting sustainable heart-healthy diets.”
The study had no commercial funding. Dr. Juul and coauthors, Dr. Ostfeld, and Ms. Allen had no disclosures.
Eating ultraprocessed foods poses a significant risk to cardiovascular and coronary heart health, according to prospective data from about 3,000 people in the Framingham Offspring Cohort, the second generation of participants in the Framingham Heart Study.
Each regular, daily serving of ultraprocessed food was linked with significant elevations of 5%-9% in the relative rates of “hard” cardiovascular disease (CVD) events, hard coronary heart disease (CHD) events, overall CVD events, and CVD death, after adjustments for numerous potential confounders including energy intake, body mass index, waist circumference, and blood pressure, Filippa Juul, PhD, and associates wrote in a report published in the Journal of the American College of Cardiology.
“Consumption of ultraprocessed foods makes up over half of the daily calories in the average American diet and are increasingly consumed worldwide. As poor diet is a major modifiable risk factor for heart disease, it represents a critical target in prevention efforts,” said Dr. Juul, a nutritional epidemiologist at New York University, in a statement released by the American College of Cardiology.
“Our findings add to a growing body of evidence suggesting cardiovascular benefits of limiting ultraprocessed foods. Ultraprocessed foods are ubiquitous and include many foods that are marketed as healthy, such as protein bars, breakfast cereals, and most industrially produced breads,” she added. Other commonplace members of the ultraprocessed food group include carbonated soft drinks, packaged snacks, candies, sausages, margarines, and energy drinks. The concept of ultraprocessed foods as a distinct, wide-ranging, and dangerous food category first appeared in 2010, and then received an update from a United Nations panel in 2019 as what’s now called the NOVA classification system.
Ultraprocessed foods fly under the radar
“Although cardiovascular guidelines emphasize consuming minimally processed foods, such as fruits, vegetables, whole grains, and nuts, they give less attention to the importance of minimizing ultraprocessed food,” wrote Robert J. Ostfeld, MD, and Kathleen E. Allen, MS, in an editorial that accompanied the new report. This reduced attention may be because of a “paucity of studies examining the association cardiovascular outcomes and ultraprocessed foods.”
The new evidence demands new policies, educational efforts, and labeling changes, suggested Dr. Ostfeld, director of preventive cardiology at Montefiore Health System in New York, and Ms. Allen, a dietitian at the Geisel School of Medicine at Dartmouth, Hanover, N.H. “The goal should be to make the unhealthy choice the hard choice and the healthy choice the easy choice.”
The new analysis used data collected from people enrolled the Framingham Offspring Cohort, with their clinical metrics and diet information collected during 1991-1995 serving as their baseline. After excluding participants with prevalent CVD at baseline and those with incomplete follow-up of CVD events, the researchers had a cohort of 3,003 adults with an average follow-up of 18 years. At baseline, the cohort averaged 54 years of age; 55% were women, their average body mass index was 27.3 kg/m2, and about 6% had diabetes. They reported eating, on average, 7.5 servings of ultraprocessed food daily.
During follow-up, the cohort tallied 648 incident CVD events, including 251 hard CVD events (coronary death, MI, or stroke) and 163 hard CHD events (coronary death or MI), and 713 total deaths including 108 CVD deaths. Other CVD events recorded but not considered hard included heart failure, intermittent claudication, and transient ischemic attack.
In a multivariate-adjusted analysis, each average daily portion of ultraprocessed food was linked with an significant 7% relative increase in the incidence of a hard CVD event, compared with participants who ate fewer ultraprocessed food portions, and a 9% relative increase in the rate of hard CHD events, the study’s two prespecified primary outcomes. The researchers also found that each ultraprocessed serving significantly was associated with a 5% relative increased rate of total CVD events, and a 9% relative rise in CVD deaths. The analysis showed no significant association between total mortality and ultraprocessed food intake. (Average follow-up for the mortality analyses was 20 years.)
The authors also reported endpoint associations with intake of specific types of ultraprocessed foods, and found significantly increased associations specifically for portions of bread, ultraprocessed meat, salty snacks, and low-calorie soft drinks.
Convenient, omnipresent, and affordable
The authors acknowledged that the associations they found need examination in ethnically diverse populations, but nonetheless the findings “suggest the need for increased efforts to implement population-wide strategies” to lower consumption of ultraprocessed foods. “Given the convenience, omnipresence, and affordability of ultraprocessed foods, careful nutrition counseling is needed to design individualized, patient-centered, heart-healthy diets,” they concluded.
“Population-wide strategies such as taxation on sugar-sweetened beverages and other ultraprocessed foods and recommendations regarding processing levels in national dietary guidelines are needed to reduce the intake of ultraprocessed foods,” added Dr. Juul in her statement. “Of course, we must also implement policies that increase the availability, accessibility, and affordability of nutritious, minimally processed foods, especially in disadvantaged populations. At the clinical level, there is a need for increased commitment to individualized nutrition counseling for adopting sustainable heart-healthy diets.”
The study had no commercial funding. Dr. Juul and coauthors, Dr. Ostfeld, and Ms. Allen had no disclosures.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Imaging alternative to AVS could boost detection of primary aldosteronism
A noninvasive imaging method for identifying whether the source of a patient’s primary aldosteronism is from unilateral or bilateral adrenal adenomas worked as well as the standard method, invasive adrenal vein sampling, in a head-to-head comparison with 143 patients.
This noninvasive alternative, which also does not require the substantial technical expertise that AVS demands, should make assessment of adenoma laterality in patients with primary aldosteronism (PA) much more widely available and accessible, predicted Dr. Wu, a researcher at Queen Mary University of London.
“It will allow more places to do this, and I think it will definitely allow more patients to be diagnosed” with PA from a unilateral source. AVS “is a real bottleneck,” she said. “We hope metomidate, or molecular imaging using other selective radiotracers, will enable many more patients to be diagnosed and appropriately managed.” Creating new diagnostic options for patients with PA and potentially increasing the number of these patients who are surgical candidates “is the aim of this study.”
Patients with PA develop a curable form of hypertension if their excess aldosterone can be neutralized with a mineralocorticoid receptor antagonist (MRA), or even more definitively by surgical removal of the adrenal aldosteronoma generating the hormonal excess as long as the adenoma is unilateral. Conventional imaging of the adrenals with CT or MRI has proven unreliable for identifying adrenal nodules noninvasively, which has made the invasive and technically challenging standard option of AVS the only game in town.
But some endocrinologists caution that the results from this one study do not suffice to make 11C-metomidate-based PET-CT imaging a widely used alternative.
‘This is a first step.’
“This study is a first step. It will take lots more data for endocrinologists to buy into a scan over AVS,” commented David A. D’Alessio, MD, professor and chief of the division of endocrinology and metabolism at Duke University in Durham, N.C.
But Dr. D’Alessio also acknowledged the clear benefits from a safe and effective alternative to AVS.
“A reliable, less invasive, and less technical means of lateralizing excess aldosterone production would increase the number of people [with a unilateral PA source] going to surgery. The reality is that, if you are not a patient at the Mayo Clinic . . .or the National Institutes of Health, then AVS is a bit of crap shoot” that is very operator and institution dependent for its accuracy, Dr. D’Alessio said in an interview.
Metomidate specifically binds to key enzymes of the adrenal corticosteroid biosynthetic pathway, making it a precise targeting agent for a radioactive tag as documented almost a decade ago. One limitation is that this radiotracer labeling of metomidate has a 20-minute half life, which means it must be produced on site, thereby making the technology out of reach for locations that can’t set up this capability.
MATCHing imaging against AVS
To test the clinical utility of metomidate-based PET-CT directly against AVS, Dr. Wu and her associates enrolled 143 adults with confirmed PA and hypertension at two centers in London and one in Cambridge, England. The MATCH study cohort averaged 53 years of age; two-thirds were men, 58% were White, and 30% were Black. Their median blood pressure was 147/91 mm Hg, and they were maintained on a median of two antihypertensive drugs.
The researchers assessed every patient with both the imaging method and AVS, performed in random order and blindly scored. They then began each patient on a 1-month regimen with an MRA (usually spironolactone but eplerenone [Inspra] was also an option) to test the responsiveness of each patient’s hypertension to this drug class and to gauge their likely response to adrenalectomy. After the MRA test, the researchers assessed the lateralization tests and determined that 78 patients were appropriate candidates for unilateral adrenalectomy while the remaining 65 patients were not and continued on the MRA regimen. They recommended surgery if patients were clear positives by AVS, by PET-CT imaging, or both.
The study had four primary outcomes to assess the ability of the two diagnostic methods to predict the success of surgery based on four increasingly stringent postsurgical criteria calculated in hierarchical sequence: Partial or complete biochemical success, complete biochemical success, partial or complete clinical success (partial meaning any significant reduction in blood pressure), or complete clinical success (systolic pressure reduced to less than 135 mm Hg). Only one of the 78 patients treated with surgery failed to achieve at least a partial biochemical response.
For each of the four metrics, 11C-metomidate PET-CT produced point estimates of diagnostic accuracy that consistently edged out AVS. While these advantages were not large enough to meet the prespecified threshold for proving superiority, they comfortably showed the noninferiority of this imaging method compared with AVS.
For example, the PET-CT method had 43.6% accuracy for predicting a clinical cure, compared with 39.7% accuracy for AVS. For complete biochemical cure, imaging had 68.8% accuracy, compared with 62.3% for AVS, Dr. Wu reported.
Another notable finding from the study was how strongly a robust blood pressure response to spironolactone predicted the clinical outcome from surgery. Patients whose systolic blood pressure fell below 135 mm Hg on MRA treatment had a nearly 18-fold higher rate of achieving a complete clinical cure following surgery compared with patients who did not have as dramatic a blood pressure response to MRA treatment.
Woefully low rates of PA assessment
But regardless of the success that PET-CT imaging has for identifying surgical candidates, the first step is to identify patients with PA, a diagnosis that’s woefully underperformed worldwide. One example: A separate report at ENDO 2021 retrospectively reviewed nearly 12,000 patients with hypertension and an indication of PA, such as treatment-resistant hypertension or early-onset hypertension, and managed at either of two university outpatient clinics in Michigan during 2010-2019. The report documented that 3% underwent PA assessment.
Diagnosis of patients with PA “is a major problem,” noted Dr. D’Alessio. “I think of PA as an underdiagnosed and undertreated condition, with a huge impact on morbidity and mortality. Any advance in this area is likely to be useful.” But, he added, “I’m dubious whether this [new imaging approach] will increase diagnosis of PA.” What’s needed is “getting more primary care physicians to do more screening” for PA among their patients with hypertension and a suggestion of a PA cause.
“Surgical cures are glamorous, but medical management is also very effective, and we have good, inexpensive drugs to do this,” the MRAs, Dr. D’Alessio said.
The study received no commercial funding. Dr. Wu and her coauthors had no disclosures. Dr. D’Alessio has been a speaker on behalf of Novo Nordisk, a consultant to Intarcia and Lilly, and has received research funding from Lilly and Merck.
A noninvasive imaging method for identifying whether the source of a patient’s primary aldosteronism is from unilateral or bilateral adrenal adenomas worked as well as the standard method, invasive adrenal vein sampling, in a head-to-head comparison with 143 patients.
This noninvasive alternative, which also does not require the substantial technical expertise that AVS demands, should make assessment of adenoma laterality in patients with primary aldosteronism (PA) much more widely available and accessible, predicted Dr. Wu, a researcher at Queen Mary University of London.
“It will allow more places to do this, and I think it will definitely allow more patients to be diagnosed” with PA from a unilateral source. AVS “is a real bottleneck,” she said. “We hope metomidate, or molecular imaging using other selective radiotracers, will enable many more patients to be diagnosed and appropriately managed.” Creating new diagnostic options for patients with PA and potentially increasing the number of these patients who are surgical candidates “is the aim of this study.”
Patients with PA develop a curable form of hypertension if their excess aldosterone can be neutralized with a mineralocorticoid receptor antagonist (MRA), or even more definitively by surgical removal of the adrenal aldosteronoma generating the hormonal excess as long as the adenoma is unilateral. Conventional imaging of the adrenals with CT or MRI has proven unreliable for identifying adrenal nodules noninvasively, which has made the invasive and technically challenging standard option of AVS the only game in town.
But some endocrinologists caution that the results from this one study do not suffice to make 11C-metomidate-based PET-CT imaging a widely used alternative.
‘This is a first step.’
“This study is a first step. It will take lots more data for endocrinologists to buy into a scan over AVS,” commented David A. D’Alessio, MD, professor and chief of the division of endocrinology and metabolism at Duke University in Durham, N.C.
But Dr. D’Alessio also acknowledged the clear benefits from a safe and effective alternative to AVS.
“A reliable, less invasive, and less technical means of lateralizing excess aldosterone production would increase the number of people [with a unilateral PA source] going to surgery. The reality is that, if you are not a patient at the Mayo Clinic . . .or the National Institutes of Health, then AVS is a bit of crap shoot” that is very operator and institution dependent for its accuracy, Dr. D’Alessio said in an interview.
Metomidate specifically binds to key enzymes of the adrenal corticosteroid biosynthetic pathway, making it a precise targeting agent for a radioactive tag as documented almost a decade ago. One limitation is that this radiotracer labeling of metomidate has a 20-minute half life, which means it must be produced on site, thereby making the technology out of reach for locations that can’t set up this capability.
MATCHing imaging against AVS
To test the clinical utility of metomidate-based PET-CT directly against AVS, Dr. Wu and her associates enrolled 143 adults with confirmed PA and hypertension at two centers in London and one in Cambridge, England. The MATCH study cohort averaged 53 years of age; two-thirds were men, 58% were White, and 30% were Black. Their median blood pressure was 147/91 mm Hg, and they were maintained on a median of two antihypertensive drugs.
The researchers assessed every patient with both the imaging method and AVS, performed in random order and blindly scored. They then began each patient on a 1-month regimen with an MRA (usually spironolactone but eplerenone [Inspra] was also an option) to test the responsiveness of each patient’s hypertension to this drug class and to gauge their likely response to adrenalectomy. After the MRA test, the researchers assessed the lateralization tests and determined that 78 patients were appropriate candidates for unilateral adrenalectomy while the remaining 65 patients were not and continued on the MRA regimen. They recommended surgery if patients were clear positives by AVS, by PET-CT imaging, or both.
The study had four primary outcomes to assess the ability of the two diagnostic methods to predict the success of surgery based on four increasingly stringent postsurgical criteria calculated in hierarchical sequence: Partial or complete biochemical success, complete biochemical success, partial or complete clinical success (partial meaning any significant reduction in blood pressure), or complete clinical success (systolic pressure reduced to less than 135 mm Hg). Only one of the 78 patients treated with surgery failed to achieve at least a partial biochemical response.
For each of the four metrics, 11C-metomidate PET-CT produced point estimates of diagnostic accuracy that consistently edged out AVS. While these advantages were not large enough to meet the prespecified threshold for proving superiority, they comfortably showed the noninferiority of this imaging method compared with AVS.
For example, the PET-CT method had 43.6% accuracy for predicting a clinical cure, compared with 39.7% accuracy for AVS. For complete biochemical cure, imaging had 68.8% accuracy, compared with 62.3% for AVS, Dr. Wu reported.
Another notable finding from the study was how strongly a robust blood pressure response to spironolactone predicted the clinical outcome from surgery. Patients whose systolic blood pressure fell below 135 mm Hg on MRA treatment had a nearly 18-fold higher rate of achieving a complete clinical cure following surgery compared with patients who did not have as dramatic a blood pressure response to MRA treatment.
Woefully low rates of PA assessment
But regardless of the success that PET-CT imaging has for identifying surgical candidates, the first step is to identify patients with PA, a diagnosis that’s woefully underperformed worldwide. One example: A separate report at ENDO 2021 retrospectively reviewed nearly 12,000 patients with hypertension and an indication of PA, such as treatment-resistant hypertension or early-onset hypertension, and managed at either of two university outpatient clinics in Michigan during 2010-2019. The report documented that 3% underwent PA assessment.
Diagnosis of patients with PA “is a major problem,” noted Dr. D’Alessio. “I think of PA as an underdiagnosed and undertreated condition, with a huge impact on morbidity and mortality. Any advance in this area is likely to be useful.” But, he added, “I’m dubious whether this [new imaging approach] will increase diagnosis of PA.” What’s needed is “getting more primary care physicians to do more screening” for PA among their patients with hypertension and a suggestion of a PA cause.
“Surgical cures are glamorous, but medical management is also very effective, and we have good, inexpensive drugs to do this,” the MRAs, Dr. D’Alessio said.
The study received no commercial funding. Dr. Wu and her coauthors had no disclosures. Dr. D’Alessio has been a speaker on behalf of Novo Nordisk, a consultant to Intarcia and Lilly, and has received research funding from Lilly and Merck.
A noninvasive imaging method for identifying whether the source of a patient’s primary aldosteronism is from unilateral or bilateral adrenal adenomas worked as well as the standard method, invasive adrenal vein sampling, in a head-to-head comparison with 143 patients.
This noninvasive alternative, which also does not require the substantial technical expertise that AVS demands, should make assessment of adenoma laterality in patients with primary aldosteronism (PA) much more widely available and accessible, predicted Dr. Wu, a researcher at Queen Mary University of London.
“It will allow more places to do this, and I think it will definitely allow more patients to be diagnosed” with PA from a unilateral source. AVS “is a real bottleneck,” she said. “We hope metomidate, or molecular imaging using other selective radiotracers, will enable many more patients to be diagnosed and appropriately managed.” Creating new diagnostic options for patients with PA and potentially increasing the number of these patients who are surgical candidates “is the aim of this study.”
Patients with PA develop a curable form of hypertension if their excess aldosterone can be neutralized with a mineralocorticoid receptor antagonist (MRA), or even more definitively by surgical removal of the adrenal aldosteronoma generating the hormonal excess as long as the adenoma is unilateral. Conventional imaging of the adrenals with CT or MRI has proven unreliable for identifying adrenal nodules noninvasively, which has made the invasive and technically challenging standard option of AVS the only game in town.
But some endocrinologists caution that the results from this one study do not suffice to make 11C-metomidate-based PET-CT imaging a widely used alternative.
‘This is a first step.’
“This study is a first step. It will take lots more data for endocrinologists to buy into a scan over AVS,” commented David A. D’Alessio, MD, professor and chief of the division of endocrinology and metabolism at Duke University in Durham, N.C.
But Dr. D’Alessio also acknowledged the clear benefits from a safe and effective alternative to AVS.
“A reliable, less invasive, and less technical means of lateralizing excess aldosterone production would increase the number of people [with a unilateral PA source] going to surgery. The reality is that, if you are not a patient at the Mayo Clinic . . .or the National Institutes of Health, then AVS is a bit of crap shoot” that is very operator and institution dependent for its accuracy, Dr. D’Alessio said in an interview.
Metomidate specifically binds to key enzymes of the adrenal corticosteroid biosynthetic pathway, making it a precise targeting agent for a radioactive tag as documented almost a decade ago. One limitation is that this radiotracer labeling of metomidate has a 20-minute half life, which means it must be produced on site, thereby making the technology out of reach for locations that can’t set up this capability.
MATCHing imaging against AVS
To test the clinical utility of metomidate-based PET-CT directly against AVS, Dr. Wu and her associates enrolled 143 adults with confirmed PA and hypertension at two centers in London and one in Cambridge, England. The MATCH study cohort averaged 53 years of age; two-thirds were men, 58% were White, and 30% were Black. Their median blood pressure was 147/91 mm Hg, and they were maintained on a median of two antihypertensive drugs.
The researchers assessed every patient with both the imaging method and AVS, performed in random order and blindly scored. They then began each patient on a 1-month regimen with an MRA (usually spironolactone but eplerenone [Inspra] was also an option) to test the responsiveness of each patient’s hypertension to this drug class and to gauge their likely response to adrenalectomy. After the MRA test, the researchers assessed the lateralization tests and determined that 78 patients were appropriate candidates for unilateral adrenalectomy while the remaining 65 patients were not and continued on the MRA regimen. They recommended surgery if patients were clear positives by AVS, by PET-CT imaging, or both.
The study had four primary outcomes to assess the ability of the two diagnostic methods to predict the success of surgery based on four increasingly stringent postsurgical criteria calculated in hierarchical sequence: Partial or complete biochemical success, complete biochemical success, partial or complete clinical success (partial meaning any significant reduction in blood pressure), or complete clinical success (systolic pressure reduced to less than 135 mm Hg). Only one of the 78 patients treated with surgery failed to achieve at least a partial biochemical response.
For each of the four metrics, 11C-metomidate PET-CT produced point estimates of diagnostic accuracy that consistently edged out AVS. While these advantages were not large enough to meet the prespecified threshold for proving superiority, they comfortably showed the noninferiority of this imaging method compared with AVS.
For example, the PET-CT method had 43.6% accuracy for predicting a clinical cure, compared with 39.7% accuracy for AVS. For complete biochemical cure, imaging had 68.8% accuracy, compared with 62.3% for AVS, Dr. Wu reported.
Another notable finding from the study was how strongly a robust blood pressure response to spironolactone predicted the clinical outcome from surgery. Patients whose systolic blood pressure fell below 135 mm Hg on MRA treatment had a nearly 18-fold higher rate of achieving a complete clinical cure following surgery compared with patients who did not have as dramatic a blood pressure response to MRA treatment.
Woefully low rates of PA assessment
But regardless of the success that PET-CT imaging has for identifying surgical candidates, the first step is to identify patients with PA, a diagnosis that’s woefully underperformed worldwide. One example: A separate report at ENDO 2021 retrospectively reviewed nearly 12,000 patients with hypertension and an indication of PA, such as treatment-resistant hypertension or early-onset hypertension, and managed at either of two university outpatient clinics in Michigan during 2010-2019. The report documented that 3% underwent PA assessment.
Diagnosis of patients with PA “is a major problem,” noted Dr. D’Alessio. “I think of PA as an underdiagnosed and undertreated condition, with a huge impact on morbidity and mortality. Any advance in this area is likely to be useful.” But, he added, “I’m dubious whether this [new imaging approach] will increase diagnosis of PA.” What’s needed is “getting more primary care physicians to do more screening” for PA among their patients with hypertension and a suggestion of a PA cause.
“Surgical cures are glamorous, but medical management is also very effective, and we have good, inexpensive drugs to do this,” the MRAs, Dr. D’Alessio said.
The study received no commercial funding. Dr. Wu and her coauthors had no disclosures. Dr. D’Alessio has been a speaker on behalf of Novo Nordisk, a consultant to Intarcia and Lilly, and has received research funding from Lilly and Merck.
FROM ENDO 2021
Dose-related AFib risk with omega-3 fatty acids?
There may be a dose-related risk for atrial fibrillation (AFib) with omega-3 fatty acid intake, data from four randomized clinical trials suggest.
The latest trial to evaluate the association, the VITAL-RHYTHM study, showed that using a low dose of omega-3 fatty acids or a vitamin D supplement had no significant effect on the risks of developing incident AFib.
The trial, first reported at last year’s American Heart Association meeting, was published online March 16 in the Journal of the American Medical Association.
Together with three other randomized clinical trials, however, these results suggest a possible dose-related effect of omega-3 fatty acids on the risk for AFib, an accompanying “Editor’s Note” suggests.
The note, by JAMA deputy editor Gregory Curfman, MD, points out that in the past 2 years, four randomized clinical trials have provided data on the risk of AFib with omega-3 fatty acid intake.
In the STRENGTH and REDUCE-IT trials, both of which evaluated high doses (4 g/day) of omega-3 fatty acids in patients with heart disease (or at high risk for it), there was a highly statistically significant increase in risk for AFib in the omega-3 groups vs. controls in both trials.
In the OMEMI trial in elderly patients with a recent myocardial infarction, an intermediate dose (1.8 g/day) of omega-3 fatty acids also showed an increase in AFib risk (hazard ratio, 1.84) but this was not significant. And now, the VITAL-RHYTHM trial shows no significant effect of a low dose (840 mg/day) of omega-3 fatty acids on the risk of developing AFib in a primary prevention population.
“Patients who choose to take omega-3 fatty acids, especially in high doses, should be informed of the risk of AF [AFib] and followed up for the possible development of this common and potentially hazardous arrhythmia,” Dr. Curfman concludes.
The authors of the VITAL-RHYTHM trial, led by Christine M. Albert, MD, MPH, Cedars-Sinai Medical Center, Los Angeles, Calif., explain that the trial was conducted after observational studies had shown that individuals with low blood levels of omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and vitamin D3 have higher risks of incident AFib, but data on dietary or supplemental intake of these nutrients on AFib risk were mixed.
“To our knowledge, this study is the first randomized, placebo-controlled trial to prospectively test the effect of any intervention on incident AF and is the only trial to test alternative upstream preventive agents for AF in a large enough population over a long enough time period to provide an assessment of the plausible benefits and risks,” they write.
The VITAL-RHYTHM study was an ancillary trial embedded within the Vitamin D and Omega-3 (VITAL) trial, which used a 2 x 2 factorial design to evaluate daily supplementation with 2,000 IU of vitamin D3 and/or 840 mg of marine omega-3 fatty acids (460 mg EPA and 380 mg DHA), in the primary prevention of cardiovascular disease and cancer in 25,871 men and women age 50 and older in the United States.
Results showed that over a median 5.3 years of treatment and follow-up, the primary endpoint of incident AFib occurred in 3.6% of the study population. For the omega-3 part of the trial, incident AFib events occurred in 3.7% of patients taking EPA/DHA vs. 3.4% of the placebo group, giving a hazard ratio of 1.09, which was not significant (P = .19).
For the vitamin D3 vs. placebo comparison, results were very similar, with incident AFib events occurring in 3.7% vs. 3.4% of participants, respectively, giving a hazard ratio of 1.09, which was again not significant (P = .19). There was no evidence for interaction between the two study agents.
“Overall, these findings do not support the use of supplemental EPA-DHA or vitamin D3 for the primary prevention of AFib and provide reassurance regarding lack of a major risk of AFib incidence associated with these commonly used supplements at these doses,” the authors conclude.
Noting that significant increases in AFib have been seen with much higher doses of omega-3 fatty acids in the REDUCE-IT and STRENGTH trials, they add: “Potentially, the adverse effect on AF risk may be dose related, and the higher dosages of EPA used in these other studies might account for the significant adverse effect on AF.”
The researchers say that, to their knowledge, this is the only randomized trial to assess the effect of vitamin D3 supplementation on AFib risk and results suggest a null effect. They add that subgroup analyses in patients with vitamin D levels considered deficient (<20 ng/mL) did not suggest a benefit; however, the power to detect a benefit in this much smaller subset of the population was limited.
They point out that, while there were no significant differences in incident AFib for either omega-3 fatty acid or vitamin D in the overall study population, an increased risk for incident AFib associated with randomized treatment was observed in selected subgroups.
For omega-3 fatty acids, AFib risk was modestly increased in taller individuals, and for vitamin D3, elevations in AFib risk were observed in younger individuals and participants who drank less alcohol.
“Although the hazard ratios and tests for interaction were significant, the P values associated with these subgroup analyses have not been adjusted for multiple comparisons. Thus, these findings should be interpreted with caution and considered hypothesis generating,” they warn.
The VITAL Rhythm Study was supported by a grant from the National Heart, Lung, and Blood Institute. Dr. Albert reported receipt of grants from St Jude Medical, Abbott, and Roche Diagnostics. Dr. Curfman reports no relevant disclosures.
A version of this article first appeared on Medscape.com.
There may be a dose-related risk for atrial fibrillation (AFib) with omega-3 fatty acid intake, data from four randomized clinical trials suggest.
The latest trial to evaluate the association, the VITAL-RHYTHM study, showed that using a low dose of omega-3 fatty acids or a vitamin D supplement had no significant effect on the risks of developing incident AFib.
The trial, first reported at last year’s American Heart Association meeting, was published online March 16 in the Journal of the American Medical Association.
Together with three other randomized clinical trials, however, these results suggest a possible dose-related effect of omega-3 fatty acids on the risk for AFib, an accompanying “Editor’s Note” suggests.
The note, by JAMA deputy editor Gregory Curfman, MD, points out that in the past 2 years, four randomized clinical trials have provided data on the risk of AFib with omega-3 fatty acid intake.
In the STRENGTH and REDUCE-IT trials, both of which evaluated high doses (4 g/day) of omega-3 fatty acids in patients with heart disease (or at high risk for it), there was a highly statistically significant increase in risk for AFib in the omega-3 groups vs. controls in both trials.
In the OMEMI trial in elderly patients with a recent myocardial infarction, an intermediate dose (1.8 g/day) of omega-3 fatty acids also showed an increase in AFib risk (hazard ratio, 1.84) but this was not significant. And now, the VITAL-RHYTHM trial shows no significant effect of a low dose (840 mg/day) of omega-3 fatty acids on the risk of developing AFib in a primary prevention population.
“Patients who choose to take omega-3 fatty acids, especially in high doses, should be informed of the risk of AF [AFib] and followed up for the possible development of this common and potentially hazardous arrhythmia,” Dr. Curfman concludes.
The authors of the VITAL-RHYTHM trial, led by Christine M. Albert, MD, MPH, Cedars-Sinai Medical Center, Los Angeles, Calif., explain that the trial was conducted after observational studies had shown that individuals with low blood levels of omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and vitamin D3 have higher risks of incident AFib, but data on dietary or supplemental intake of these nutrients on AFib risk were mixed.
“To our knowledge, this study is the first randomized, placebo-controlled trial to prospectively test the effect of any intervention on incident AF and is the only trial to test alternative upstream preventive agents for AF in a large enough population over a long enough time period to provide an assessment of the plausible benefits and risks,” they write.
The VITAL-RHYTHM study was an ancillary trial embedded within the Vitamin D and Omega-3 (VITAL) trial, which used a 2 x 2 factorial design to evaluate daily supplementation with 2,000 IU of vitamin D3 and/or 840 mg of marine omega-3 fatty acids (460 mg EPA and 380 mg DHA), in the primary prevention of cardiovascular disease and cancer in 25,871 men and women age 50 and older in the United States.
Results showed that over a median 5.3 years of treatment and follow-up, the primary endpoint of incident AFib occurred in 3.6% of the study population. For the omega-3 part of the trial, incident AFib events occurred in 3.7% of patients taking EPA/DHA vs. 3.4% of the placebo group, giving a hazard ratio of 1.09, which was not significant (P = .19).
For the vitamin D3 vs. placebo comparison, results were very similar, with incident AFib events occurring in 3.7% vs. 3.4% of participants, respectively, giving a hazard ratio of 1.09, which was again not significant (P = .19). There was no evidence for interaction between the two study agents.
“Overall, these findings do not support the use of supplemental EPA-DHA or vitamin D3 for the primary prevention of AFib and provide reassurance regarding lack of a major risk of AFib incidence associated with these commonly used supplements at these doses,” the authors conclude.
Noting that significant increases in AFib have been seen with much higher doses of omega-3 fatty acids in the REDUCE-IT and STRENGTH trials, they add: “Potentially, the adverse effect on AF risk may be dose related, and the higher dosages of EPA used in these other studies might account for the significant adverse effect on AF.”
The researchers say that, to their knowledge, this is the only randomized trial to assess the effect of vitamin D3 supplementation on AFib risk and results suggest a null effect. They add that subgroup analyses in patients with vitamin D levels considered deficient (<20 ng/mL) did not suggest a benefit; however, the power to detect a benefit in this much smaller subset of the population was limited.
They point out that, while there were no significant differences in incident AFib for either omega-3 fatty acid or vitamin D in the overall study population, an increased risk for incident AFib associated with randomized treatment was observed in selected subgroups.
For omega-3 fatty acids, AFib risk was modestly increased in taller individuals, and for vitamin D3, elevations in AFib risk were observed in younger individuals and participants who drank less alcohol.
“Although the hazard ratios and tests for interaction were significant, the P values associated with these subgroup analyses have not been adjusted for multiple comparisons. Thus, these findings should be interpreted with caution and considered hypothesis generating,” they warn.
The VITAL Rhythm Study was supported by a grant from the National Heart, Lung, and Blood Institute. Dr. Albert reported receipt of grants from St Jude Medical, Abbott, and Roche Diagnostics. Dr. Curfman reports no relevant disclosures.
A version of this article first appeared on Medscape.com.
There may be a dose-related risk for atrial fibrillation (AFib) with omega-3 fatty acid intake, data from four randomized clinical trials suggest.
The latest trial to evaluate the association, the VITAL-RHYTHM study, showed that using a low dose of omega-3 fatty acids or a vitamin D supplement had no significant effect on the risks of developing incident AFib.
The trial, first reported at last year’s American Heart Association meeting, was published online March 16 in the Journal of the American Medical Association.
Together with three other randomized clinical trials, however, these results suggest a possible dose-related effect of omega-3 fatty acids on the risk for AFib, an accompanying “Editor’s Note” suggests.
The note, by JAMA deputy editor Gregory Curfman, MD, points out that in the past 2 years, four randomized clinical trials have provided data on the risk of AFib with omega-3 fatty acid intake.
In the STRENGTH and REDUCE-IT trials, both of which evaluated high doses (4 g/day) of omega-3 fatty acids in patients with heart disease (or at high risk for it), there was a highly statistically significant increase in risk for AFib in the omega-3 groups vs. controls in both trials.
In the OMEMI trial in elderly patients with a recent myocardial infarction, an intermediate dose (1.8 g/day) of omega-3 fatty acids also showed an increase in AFib risk (hazard ratio, 1.84) but this was not significant. And now, the VITAL-RHYTHM trial shows no significant effect of a low dose (840 mg/day) of omega-3 fatty acids on the risk of developing AFib in a primary prevention population.
“Patients who choose to take omega-3 fatty acids, especially in high doses, should be informed of the risk of AF [AFib] and followed up for the possible development of this common and potentially hazardous arrhythmia,” Dr. Curfman concludes.
The authors of the VITAL-RHYTHM trial, led by Christine M. Albert, MD, MPH, Cedars-Sinai Medical Center, Los Angeles, Calif., explain that the trial was conducted after observational studies had shown that individuals with low blood levels of omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and vitamin D3 have higher risks of incident AFib, but data on dietary or supplemental intake of these nutrients on AFib risk were mixed.
“To our knowledge, this study is the first randomized, placebo-controlled trial to prospectively test the effect of any intervention on incident AF and is the only trial to test alternative upstream preventive agents for AF in a large enough population over a long enough time period to provide an assessment of the plausible benefits and risks,” they write.
The VITAL-RHYTHM study was an ancillary trial embedded within the Vitamin D and Omega-3 (VITAL) trial, which used a 2 x 2 factorial design to evaluate daily supplementation with 2,000 IU of vitamin D3 and/or 840 mg of marine omega-3 fatty acids (460 mg EPA and 380 mg DHA), in the primary prevention of cardiovascular disease and cancer in 25,871 men and women age 50 and older in the United States.
Results showed that over a median 5.3 years of treatment and follow-up, the primary endpoint of incident AFib occurred in 3.6% of the study population. For the omega-3 part of the trial, incident AFib events occurred in 3.7% of patients taking EPA/DHA vs. 3.4% of the placebo group, giving a hazard ratio of 1.09, which was not significant (P = .19).
For the vitamin D3 vs. placebo comparison, results were very similar, with incident AFib events occurring in 3.7% vs. 3.4% of participants, respectively, giving a hazard ratio of 1.09, which was again not significant (P = .19). There was no evidence for interaction between the two study agents.
“Overall, these findings do not support the use of supplemental EPA-DHA or vitamin D3 for the primary prevention of AFib and provide reassurance regarding lack of a major risk of AFib incidence associated with these commonly used supplements at these doses,” the authors conclude.
Noting that significant increases in AFib have been seen with much higher doses of omega-3 fatty acids in the REDUCE-IT and STRENGTH trials, they add: “Potentially, the adverse effect on AF risk may be dose related, and the higher dosages of EPA used in these other studies might account for the significant adverse effect on AF.”
The researchers say that, to their knowledge, this is the only randomized trial to assess the effect of vitamin D3 supplementation on AFib risk and results suggest a null effect. They add that subgroup analyses in patients with vitamin D levels considered deficient (<20 ng/mL) did not suggest a benefit; however, the power to detect a benefit in this much smaller subset of the population was limited.
They point out that, while there were no significant differences in incident AFib for either omega-3 fatty acid or vitamin D in the overall study population, an increased risk for incident AFib associated with randomized treatment was observed in selected subgroups.
For omega-3 fatty acids, AFib risk was modestly increased in taller individuals, and for vitamin D3, elevations in AFib risk were observed in younger individuals and participants who drank less alcohol.
“Although the hazard ratios and tests for interaction were significant, the P values associated with these subgroup analyses have not been adjusted for multiple comparisons. Thus, these findings should be interpreted with caution and considered hypothesis generating,” they warn.
The VITAL Rhythm Study was supported by a grant from the National Heart, Lung, and Blood Institute. Dr. Albert reported receipt of grants from St Jude Medical, Abbott, and Roche Diagnostics. Dr. Curfman reports no relevant disclosures.
A version of this article first appeared on Medscape.com.
Cardiac rehab after cardiac valve surgery associated with reduced mortality
Background: National guidelines recommend CR after CVS. However, neither enrollment in CR nor its benefits have been well described in this population.
Study design: Observational cohort study.
Setting: Enrolled Medicare beneficiaries residing in the United States in 2014.
Synopsis: There were 41,369 Medicare patients who underwent CVS and met the study requirements; of these, 43.2% enrolled in CR programs. Those who had concomitant coronary artery bypass grafting (CABG) surgery or who resided in the Midwest region of the United States were more likely to enroll in CR. Asian, black, and Hispanic patients were less likely to enroll in CR. Enrollment in CR after CVS was associated with a decreased risk of 1-year hospitalization (hazard ratio, 0.66; 95% confidence interval, 0.63-0.69). CR utilization was also associated with a decrease in 1-year mortality after CVS (HR, 0.39; 95% CI, 0.35-0.44).
Enrollment rates in CR after CVS were lower than that of heart transplant patients, but higher than that for patients with systolic heart failure or after CABG. Major study limitations were the lack of generalizability to younger patients because all patients examined were older than 64 years.
Bottom line: Racial and geographic factors influence the rate of enrollment in CR for patients undergoing CVS. All patients should be encouraged to participate in CR after CVS because it is associated with reduced 1-year mortality and risk of hospitalization.
Citation: Patel DK et. al. Association of cardiac rehabilitation with decreased hospitalization and mortality risk after cardiac valve surgery. JAMA Cardiol. 2019 Oct 23. doi: 10.1001/jamacardio.2019.4032.
Dr. Babbel is a hospitalist and assistant professor of medicine at the University of Utah, Salt Lake City.
Background: National guidelines recommend CR after CVS. However, neither enrollment in CR nor its benefits have been well described in this population.
Study design: Observational cohort study.
Setting: Enrolled Medicare beneficiaries residing in the United States in 2014.
Synopsis: There were 41,369 Medicare patients who underwent CVS and met the study requirements; of these, 43.2% enrolled in CR programs. Those who had concomitant coronary artery bypass grafting (CABG) surgery or who resided in the Midwest region of the United States were more likely to enroll in CR. Asian, black, and Hispanic patients were less likely to enroll in CR. Enrollment in CR after CVS was associated with a decreased risk of 1-year hospitalization (hazard ratio, 0.66; 95% confidence interval, 0.63-0.69). CR utilization was also associated with a decrease in 1-year mortality after CVS (HR, 0.39; 95% CI, 0.35-0.44).
Enrollment rates in CR after CVS were lower than that of heart transplant patients, but higher than that for patients with systolic heart failure or after CABG. Major study limitations were the lack of generalizability to younger patients because all patients examined were older than 64 years.
Bottom line: Racial and geographic factors influence the rate of enrollment in CR for patients undergoing CVS. All patients should be encouraged to participate in CR after CVS because it is associated with reduced 1-year mortality and risk of hospitalization.
Citation: Patel DK et. al. Association of cardiac rehabilitation with decreased hospitalization and mortality risk after cardiac valve surgery. JAMA Cardiol. 2019 Oct 23. doi: 10.1001/jamacardio.2019.4032.
Dr. Babbel is a hospitalist and assistant professor of medicine at the University of Utah, Salt Lake City.
Background: National guidelines recommend CR after CVS. However, neither enrollment in CR nor its benefits have been well described in this population.
Study design: Observational cohort study.
Setting: Enrolled Medicare beneficiaries residing in the United States in 2014.
Synopsis: There were 41,369 Medicare patients who underwent CVS and met the study requirements; of these, 43.2% enrolled in CR programs. Those who had concomitant coronary artery bypass grafting (CABG) surgery or who resided in the Midwest region of the United States were more likely to enroll in CR. Asian, black, and Hispanic patients were less likely to enroll in CR. Enrollment in CR after CVS was associated with a decreased risk of 1-year hospitalization (hazard ratio, 0.66; 95% confidence interval, 0.63-0.69). CR utilization was also associated with a decrease in 1-year mortality after CVS (HR, 0.39; 95% CI, 0.35-0.44).
Enrollment rates in CR after CVS were lower than that of heart transplant patients, but higher than that for patients with systolic heart failure or after CABG. Major study limitations were the lack of generalizability to younger patients because all patients examined were older than 64 years.
Bottom line: Racial and geographic factors influence the rate of enrollment in CR for patients undergoing CVS. All patients should be encouraged to participate in CR after CVS because it is associated with reduced 1-year mortality and risk of hospitalization.
Citation: Patel DK et. al. Association of cardiac rehabilitation with decreased hospitalization and mortality risk after cardiac valve surgery. JAMA Cardiol. 2019 Oct 23. doi: 10.1001/jamacardio.2019.4032.
Dr. Babbel is a hospitalist and assistant professor of medicine at the University of Utah, Salt Lake City.